diff --git a/docs/file-based-configuration.md b/docs/file-based-configuration.md
index e779ba1e85..1c662dc2c6 100644
--- a/docs/file-based-configuration.md
+++ b/docs/file-based-configuration.md
@@ -81,4 +81,21 @@ resource:
       operatingsystem: # Detects OS-level attributes (os.*)
       process:         # Detects process-level attributes (process.*)
       processruntime:  # Detects process runtime attributes (process.runtime.*)
-```  
+```
+
+### Plugins Configuration
+
+For more details and updates about Plugins Configuration, see:
+[Plugins documentation](plugins.md)
+
+``` yaml
+plugins/development:
+  # Configure plugins. Entries have higher priority than entries from .plugins_list.
+  # List of plugins to load. Each entry is the full type name, followed by the assembly name.
+  # For example: MyNamespace.MyPlugin, MyAssembly, Version=1.0.0, Culture=neutral, PublicKeyToken=null
+  plugins:
+    - Test1.Plugins.Plugin, Test1.Plugins, Version=1.0.0, Culture=neutral, PublicKeyToken=null
+    - Test2.Plugins.Plugin, Test2.Plugins
+  # Alternatively, configure via a colon-separated list (same format as OTEL_DOTNET_AUTO_PLUGINS).
+  plugins_list: ${OTEL_DOTNET_AUTO_PLUGINS}
+```
diff --git a/src/OpenTelemetry.AutoInstrumentation/Configurations/FileBasedConfiguration/PluginsConfiguration.cs b/src/OpenTelemetry.AutoInstrumentation/Configurations/FileBasedConfiguration/PluginsConfiguration.cs
new file mode 100644
index 0000000000..e3b9bd2eda
--- /dev/null
+++ b/src/OpenTelemetry.AutoInstrumentation/Configurations/FileBasedConfiguration/PluginsConfiguration.cs
@@ -0,0 +1,47 @@
+// Copyright The OpenTelemetry Authors
+// SPDX-License-Identifier: Apache-2.0
+
+using Vendors.YamlDotNet.Serialization;
+
+namespace OpenTelemetry.AutoInstrumentation.Configurations.FileBasedConfiguration;
+
+internal class PluginsConfiguration
+{
+    /// <summary>
+    /// Gets or sets the list of plugins.
+    /// </summary>
+    [YamlMember(Alias = "plugins")]
+    public List<string>? Plugins { get; set; }
+
+    /// <summary>
+    /// Gets or sets the plugins list.
+    /// </summary>
+    [YamlMember(Alias = "plugins_list")]
+    public string? PluginsList { get; set; }
+
+    public List<string> ParsePlugins()
+    {
+        var uniquePlugins = new HashSet<string>();
+
+        if (Plugins != null)
+        {
+            foreach (var plugin in Plugins)
+            {
+                if (!string.IsNullOrWhiteSpace(plugin))
+                {
+                    uniquePlugins.Add(plugin.Trim());
+                }
+            }
+        }
+
+        if (!string.IsNullOrWhiteSpace(PluginsList))
+        {
+            foreach (var plugin in PluginsList!.Split(Constants.ConfigurationValues.DotNetQualifiedNameSeparator))
+            {
+                uniquePlugins.Add(plugin.Trim());
+            }
+        }
+
+        return uniquePlugins.ToList();
+    }
+}
diff --git a/src/OpenTelemetry.AutoInstrumentation/Configurations/FileBasedConfiguration/YamlConfiguration.cs b/src/OpenTelemetry.AutoInstrumentation/Configurations/FileBasedConfiguration/YamlConfiguration.cs
index 62a3b94821..bde75b5426 100644
--- a/src/OpenTelemetry.AutoInstrumentation/Configurations/FileBasedConfiguration/YamlConfiguration.cs
+++ b/src/OpenTelemetry.AutoInstrumentation/Configurations/FileBasedConfiguration/YamlConfiguration.cs
@@ -49,4 +49,10 @@ internal class YamlConfiguration
     /// </summary>
     [YamlMember(Alias = "no_code/development")]
     public NoCodeConfiguration? NoCode { get; set; }
+
+    /// <summary>
+    /// Gets or sets the plugins configuration.
+    /// </summary>
+    [YamlMember(Alias = "plugins/development")]
+    public PluginsConfiguration? Plugins { get; set; }
 }
diff --git a/src/OpenTelemetry.AutoInstrumentation/Configurations/GeneralSettings.cs b/src/OpenTelemetry.AutoInstrumentation/Configurations/GeneralSettings.cs
index 5af9978bca..09ecaeb41e 100644
--- a/src/OpenTelemetry.AutoInstrumentation/Configurations/GeneralSettings.cs
+++ b/src/OpenTelemetry.AutoInstrumentation/Configurations/GeneralSettings.cs
@@ -8,11 +8,6 @@ namespace OpenTelemetry.AutoInstrumentation.Configurations;
 
 internal class GeneralSettings : Settings
 {
-    /// <summary>
-    /// Gets the list of plugins represented by <see cref="Type.AssemblyQualifiedName"/>.
-    /// </summary>
-    public IList<string> Plugins { get; } = [];
-
     /// <summary>
     /// Gets a value indicating whether the <see cref="AppDomain.UnhandledException"/> event should trigger
     /// the flushing of telemetry data.
@@ -32,15 +27,6 @@ internal class GeneralSettings : Settings
 
     protected override void OnLoadEnvVar(Configuration configuration)
     {
-        var providerPlugins = configuration.GetString(ConfigurationKeys.ProviderPlugins);
-        if (providerPlugins != null)
-        {
-            foreach (var pluginAssemblyQualifiedName in providerPlugins.Split(Constants.ConfigurationValues.DotNetQualifiedNameSeparator))
-            {
-                Plugins.Add(pluginAssemblyQualifiedName);
-            }
-        }
-
         FlushOnUnhandledException = configuration.GetBool(ConfigurationKeys.FlushOnUnhandledException) ?? false;
         SetupSdk = configuration.GetBool(ConfigurationKeys.SetupSdk) ?? true;
 
diff --git a/src/OpenTelemetry.AutoInstrumentation/Configurations/PluginsSettings.cs b/src/OpenTelemetry.AutoInstrumentation/Configurations/PluginsSettings.cs
new file mode 100644
index 0000000000..f9ce823e3f
--- /dev/null
+++ b/src/OpenTelemetry.AutoInstrumentation/Configurations/PluginsSettings.cs
@@ -0,0 +1,31 @@
+// Copyright The OpenTelemetry Authors
+// SPDX-License-Identifier: Apache-2.0
+
+using OpenTelemetry.AutoInstrumentation.Configurations.FileBasedConfiguration;
+
+namespace OpenTelemetry.AutoInstrumentation.Configurations;
+
+internal class PluginsSettings : Settings
+{
+    /// <summary>
+    /// Gets the list of plugins represented by <see cref="Type.AssemblyQualifiedName"/>.
+    /// </summary>
+    public IList<string> Plugins { get; private set; } = [];
+
+    protected override void OnLoadEnvVar(Configuration configuration)
+    {
+        var providerPlugins = configuration.GetString(ConfigurationKeys.ProviderPlugins);
+        if (providerPlugins != null)
+        {
+            foreach (var pluginAssemblyQualifiedName in providerPlugins.Split(Constants.ConfigurationValues.DotNetQualifiedNameSeparator))
+            {
+                Plugins.Add(pluginAssemblyQualifiedName);
+            }
+        }
+    }
+
+    protected override void OnLoadFile(YamlConfiguration configuration)
+    {
+        Plugins = configuration.Plugins?.ParsePlugins() ?? [];
+    }
+}
diff --git a/src/OpenTelemetry.AutoInstrumentation/Instrumentation.cs b/src/OpenTelemetry.AutoInstrumentation/Instrumentation.cs
index d781ec406a..374a6c0e37 100644
--- a/src/OpenTelemetry.AutoInstrumentation/Instrumentation.cs
+++ b/src/OpenTelemetry.AutoInstrumentation/Instrumentation.cs
@@ -69,6 +69,8 @@ internal static LoggerProvider? LoggerProvider
 
     internal static Lazy<NoCodeSettings> NoCodeSettings { get; } = new(() => Settings.FromDefaultSources<NoCodeSettings>(FailFastSettings.Value.FailFast));
 
+    internal static Lazy<PluginsSettings> PluginsSettings { get; } = new(() => Settings.FromDefaultSources<PluginsSettings>(FailFastSettings.Value.FailFast));
+
     /// <summary>
     /// Initialize the OpenTelemetry SDK with a pre-defined set of exporters, shims, and
     /// instrumentations.
@@ -102,7 +104,7 @@ public static void Initialize()
             // Initialize SdkSelfDiagnosticsEventListener to create an EventListener for the OpenTelemetry SDK
             _sdkEventListener = new(Logger);
 
-            _pluginManager = new PluginManager(GeneralSettings.Value);
+            _pluginManager = new PluginManager(PluginsSettings.Value);
             _pluginManager.Initializing();
 
             // Register to shutdown events
diff --git a/src/OpenTelemetry.AutoInstrumentation/Plugins/PluginManager.cs b/src/OpenTelemetry.AutoInstrumentation/Plugins/PluginManager.cs
index 9327dccf75..0ce6304c3b 100644
--- a/src/OpenTelemetry.AutoInstrumentation/Plugins/PluginManager.cs
+++ b/src/OpenTelemetry.AutoInstrumentation/Plugins/PluginManager.cs
@@ -13,7 +13,7 @@ internal partial class PluginManager
 {
     private readonly IReadOnlyList<(Type Type, object Instance)> _plugins;
 
-    public PluginManager(GeneralSettings settings)
+    public PluginManager(PluginsSettings settings)
     {
         var plugins = new List<(Type, object)>();
 
@@ -131,10 +131,7 @@ private void CallPlugins(string methodName)
         foreach (var plugin in _plugins)
         {
             var mi = plugin.Type.GetMethod(methodName, Type.EmptyTypes);
-            if (mi is not null)
-            {
-                mi.Invoke(plugin.Instance, null);
-            }
+            mi?.Invoke(plugin.Instance, null);
         }
     }
 
@@ -142,11 +139,8 @@ private void CallPlugins(string methodName, (Type Type, object Value) arg)
     {
         foreach (var plugin in _plugins)
         {
-            var mi = plugin.Type.GetMethod(methodName, new[] { arg.Type });
-            if (mi is not null)
-            {
-                mi.Invoke(plugin.Instance, new object[] { arg.Value });
-            }
+            var mi = plugin.Type.GetMethod(methodName, [arg.Type]);
+            mi?.Invoke(plugin.Instance, [arg.Value]);
         }
     }
 }
diff --git a/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/FilebasedPluginsSettingsTests.cs b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/FilebasedPluginsSettingsTests.cs
new file mode 100644
index 0000000000..b5a85c407b
--- /dev/null
+++ b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/FilebasedPluginsSettingsTests.cs
@@ -0,0 +1,70 @@
+// Copyright The OpenTelemetry Authors
+// SPDX-License-Identifier: Apache-2.0
+
+using OpenTelemetry.AutoInstrumentation.Configurations;
+using OpenTelemetry.AutoInstrumentation.Configurations.FileBasedConfiguration;
+using Xunit;
+
+namespace OpenTelemetry.AutoInstrumentation.Tests.Configurations.FileBased;
+
+public class FilebasedPluginsSettingsTests
+{
+    [Fact]
+    public void LoadFile_PluginsSettings()
+    {
+        var conf = new YamlConfiguration
+        {
+            Plugins = new PluginsConfiguration
+            {
+                Plugins = ["Test.Plugins.Plugin, Test.Plugins"]
+            }
+        };
+
+        var settings = new PluginsSettings();
+
+        settings.LoadFile(conf);
+
+        Assert.Single(settings.Plugins);
+        Assert.Contains("Test.Plugins.Plugin, Test.Plugins", settings.Plugins);
+    }
+
+    [Fact]
+    public void LoadFile_PluginsListSettings()
+    {
+        var conf = new YamlConfiguration
+        {
+            Plugins = new PluginsConfiguration
+            {
+                PluginsList = "Test.Plugins.Plugin, Test.Plugins"
+            }
+        };
+
+        var settings = new PluginsSettings();
+
+        settings.LoadFile(conf);
+        Assert.Single(settings.Plugins);
+        Assert.Contains("Test.Plugins.Plugin, Test.Plugins", settings.Plugins);
+    }
+
+    [Fact]
+    public void LoadFile_MergePluginsSettings()
+    {
+        var conf = new YamlConfiguration
+        {
+            Plugins = new PluginsConfiguration
+            {
+                Plugins = ["Test1.Plugins.Plugin, Test1.Plugins", "Test2.Plugins.Plugin, Test2.Plugins"],
+                PluginsList = "Test2.Plugins.Plugin, Test2.Plugins:Test3.Plugins.Plugin, Test3.Plugins"
+            }
+        };
+
+        var settings = new PluginsSettings();
+
+        settings.LoadFile(conf);
+
+        Assert.Equal(3, settings.Plugins.Count);
+        Assert.Contains("Test1.Plugins.Plugin, Test1.Plugins", settings.Plugins);
+        Assert.Contains("Test2.Plugins.Plugin, Test2.Plugins", settings.Plugins);
+        Assert.Contains("Test3.Plugins.Plugin, Test3.Plugins", settings.Plugins);
+    }
+}
diff --git a/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Files/TestPluginsFile.yaml b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Files/TestPluginsFile.yaml
new file mode 100644
index 0000000000..24cd86b41a
--- /dev/null
+++ b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Files/TestPluginsFile.yaml
@@ -0,0 +1,5 @@
+file_format: "1.0-rc.1"
+plugins/development:
+  plugins:
+    - Test1.Plugins.Plugin, Test1.Plugins
+    - Test2.Plugins.Plugin, Test2.Plugins
diff --git a/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Files/TestPluginsFileEnvVars.yaml b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Files/TestPluginsFileEnvVars.yaml
new file mode 100644
index 0000000000..340b0be923
--- /dev/null
+++ b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Files/TestPluginsFileEnvVars.yaml
@@ -0,0 +1,4 @@
+file_format: "1.0-rc.1"
+plugins/development:
+  plugins_list: ${OTEL_DOTNET_AUTO_PLUGINS}
+
diff --git a/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Parser/ParserPluginsTests.cs b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Parser/ParserPluginsTests.cs
new file mode 100644
index 0000000000..72ca77e1a6
--- /dev/null
+++ b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/FileBased/Parser/ParserPluginsTests.cs
@@ -0,0 +1,42 @@
+// Copyright The OpenTelemetry Authors
+// SPDX-License-Identifier: Apache-2.0
+
+using Xunit;
+using YamlParser = OpenTelemetry.AutoInstrumentation.Configurations.FileBasedConfiguration.Parser.Parser;
+
+namespace OpenTelemetry.AutoInstrumentation.Tests.Configurations.FileBased.Parser;
+
+[Collection("Non-Parallel Collection")]
+public class ParserPluginsTests
+{
+    [Fact]
+    public void Parse_FullConfigYaml_ShouldPopulateModelCorrectly()
+    {
+        var config = YamlParser.ParseYaml("Configurations/FileBased/Files/TestPluginsFile.yaml");
+
+        Assert.NotNull(config);
+
+        Assert.NotNull(config.Plugins);
+        Assert.NotNull(config.Plugins.Plugins);
+        Assert.Null(config.Plugins.PluginsList);
+        Assert.Equal(2, config.Plugins.Plugins.Count);
+        Assert.Equal("Test1.Plugins.Plugin, Test1.Plugins", config.Plugins.Plugins[0]);
+        Assert.Equal("Test2.Plugins.Plugin, Test2.Plugins", config.Plugins.Plugins[1]);
+    }
+
+    [Fact]
+    public void Parse_EnvVarYaml_ShouldPopulateModelCompletely()
+    {
+        Environment.SetEnvironmentVariable("OTEL_DOTNET_AUTO_PLUGINS", "Test.Plugins.Plugin, Test.Plugins");
+
+        var config = YamlParser.ParseYaml("Configurations/FileBased/Files/TestPluginsFileEnvVars.yaml");
+
+        Assert.NotNull(config);
+
+        Assert.NotNull(config.Plugins);
+        Assert.Null(config.Plugins.Plugins);
+        Assert.NotNull(config.Plugins.PluginsList);
+
+        Assert.Equal("Test.Plugins.Plugin, Test.Plugins", config.Plugins.PluginsList);
+    }
+}
diff --git a/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/PluginManagerTests.cs b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/PluginManagerTests.cs
index 2c1317b8c7..a9b7085898 100644
--- a/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/PluginManagerTests.cs
+++ b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/PluginManagerTests.cs
@@ -150,14 +150,14 @@ public void ConfigureResourceSuccess()
         Assert.Equal("value", resource.Attributes.First().Value);
     }
 
-    private static GeneralSettings GetSettings(string assemblyQualifiedName)
+    private static PluginsSettings GetSettings(string assemblyQualifiedName)
     {
         var config = new Configuration(false, new NameValueConfigurationSource(false, new NameValueCollection()
         {
             { ConfigurationKeys.ProviderPlugins, assemblyQualifiedName }
         }));
 
-        var settings = new GeneralSettings();
+        var settings = new PluginsSettings();
         settings.LoadEnvVar(config);
         return settings;
     }
diff --git a/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/SettingsTests.cs b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/SettingsTests.cs
index 1b5ebd8fab..41d65a0381 100644
--- a/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/SettingsTests.cs
+++ b/test/OpenTelemetry.AutoInstrumentation.Tests/Configurations/SettingsTests.cs
@@ -30,10 +30,17 @@ internal void GeneralSettings_DefaultValues()
     {
         var settings = Settings.FromDefaultSources<GeneralSettings>(false);
 
-        Assert.Empty(settings.Plugins);
         Assert.False(settings.FlushOnUnhandledException);
     }
 
+    [Fact]
+    internal void PluginsSettings_DefaultValues()
+    {
+        var settings = Settings.FromDefaultSources<PluginsSettings>(false);
+
+        Assert.Empty(settings.Plugins);
+    }
+
     [Fact]
     internal void ResourceSettings_DefaultValues()
     {
diff --git a/test/OpenTelemetry.AutoInstrumentation.Tests/OpenTelemetry.AutoInstrumentation.Tests.csproj b/test/OpenTelemetry.AutoInstrumentation.Tests/OpenTelemetry.AutoInstrumentation.Tests.csproj
index e34a9eb301..da6639f509 100644
--- a/test/OpenTelemetry.AutoInstrumentation.Tests/OpenTelemetry.AutoInstrumentation.Tests.csproj
+++ b/test/OpenTelemetry.AutoInstrumentation.Tests/OpenTelemetry.AutoInstrumentation.Tests.csproj
@@ -1,4 +1,4 @@
-<Project Sdk="Microsoft.NET.Sdk">
+<Project Sdk="Microsoft.NET.Sdk">
 
   <ItemGroup>
     <PackageReference Include="Newtonsoft.Json" />
@@ -15,9 +15,15 @@
     <None Update="Configurations\FileBased\Files\NoCodeFile.yaml">
       <CopyToOutputDirectory>PreserveNewest</CopyToOutputDirectory>
     </None>
+    <None Update="Configurations\FileBased\Files\TestPluginsFile.yaml">
+      <CopyToOutputDirectory>PreserveNewest</CopyToOutputDirectory>
+    </None>
     <None Update="Configurations\FileBased\Files\TestGeneralFile.yaml">
       <CopyToOutputDirectory>PreserveNewest</CopyToOutputDirectory>
     </None>
+    <None Update="Configurations\FileBased\Files\TestPluginsFileEnvVars.yaml">
+      <CopyToOutputDirectory>PreserveNewest</CopyToOutputDirectory>
+    </None>
     <None Update="Configurations\FileBased\Files\TestResourceFile.yaml">
       <CopyToOutputDirectory>PreserveNewest</CopyToOutputDirectory>
     </None>