diff --git a/docs/api_extra.rst b/docs/api_extra.rst
index 903aa586..02582d3f 100644
--- a/docs/api_extra.rst
+++ b/docs/api_extra.rst
@@ -1412,6 +1412,8 @@ functions:
                   Py_INCREF(o);
               },
               [](PyObject * o) noexcept {
+                  if (!nb::is_alive())
+                      return;
                   nb::gil_scoped_acquire guard;
                   Py_DECREF(o);
               });
@@ -1419,6 +1421,10 @@ functions:
           // ...
       }
 
+   The liveness check in the destructor is necessary in a multi-threaded
+   environment because when the interpreter is shutting down, trying to
+   (re-) take the GIL will throw a cancellation exception.
+
 .. cpp:function:: inline void inc_ref(intrusive_base * o) noexcept
 
    Reference counting helper function that calls ``o->inc_ref()`` if ``o`` is
diff --git a/docs/changelog.rst b/docs/changelog.rst
index 530a6b2a..f4f51b8a 100644
--- a/docs/changelog.rst
+++ b/docs/changelog.rst
@@ -73,6 +73,11 @@ Version TBD (not yet released)
   binding abstractions that "feel like" the built-in ones.
   (PR `#884 <https://github.com/wjakob/nanobind/pull/884>`__)
 
+- Added :cpp:func:`nb::is_alive() <is_alive>` checks to prevent destructors
+  from trying to re-acquire the GIL when the interpreter shuts down,
+  as that triggers a cancellation exception which isn't allowed in
+  destructors.
+
 Version 2.4.0 (Dec 6, 2024)
 ---------------------------
 
diff --git a/docs/ownership_adv.rst b/docs/ownership_adv.rst
index bede6974..a61c2539 100644
--- a/docs/ownership_adv.rst
+++ b/docs/ownership_adv.rst
@@ -172,6 +172,8 @@ bindings are an optional component).
            Py_INCREF(o);
        },
        [](PyObject *o) noexcept {
+           if (!nb::is_alive())
+               return;
            nb::gil_scoped_acquire guard;
            Py_DECREF(o);
        });
diff --git a/include/nanobind/intrusive/counter.h b/include/nanobind/intrusive/counter.h
index cb154644..1bd9738a 100644
--- a/include/nanobind/intrusive/counter.h
+++ b/include/nanobind/intrusive/counter.h
@@ -140,6 +140,8 @@ NAMESPACE_BEGIN(nanobind)
  *         Py_INCREF(o);
  *     },
  *     [](PyObject *o) noexcept {
+ *         if (!nb::is_alive())
+ *             return;
  *         nb::gil_scoped_acquire guard;
  *         Py_DECREF(o);
  *     });
diff --git a/include/nanobind/stl/function.h b/include/nanobind/stl/function.h
index b9623402..f5314f6e 100644
--- a/include/nanobind/stl/function.h
+++ b/include/nanobind/stl/function.h
@@ -34,7 +34,7 @@ struct pyfunc_wrapper {
     }
 
     ~pyfunc_wrapper() {
-        if (f) {
+        if (f && is_alive()) {
             gil_scoped_acquire acq;
             Py_DECREF(f);
         }
diff --git a/src/error.cpp b/src/error.cpp
index 5d1d6666..8dafc2a7 100644
--- a/src/error.cpp
+++ b/src/error.cpp
@@ -28,7 +28,7 @@ python_error::python_error() {
 }
 
 python_error::~python_error() {
-    if (m_value) {
+    if (m_value && detail::is_alive()) {
         gil_scoped_acquire acq;
         /* With GIL held */ {
             // Clear error status in case the following executes Python code
@@ -73,7 +73,7 @@ python_error::python_error() {
 }
 
 python_error::~python_error() {
-    if (m_type) {
+    if (m_type && detail::is_alive()) {
         gil_scoped_acquire acq;
         /* With GIL held */ {
             // Clear error status in case the following executes Python code
diff --git a/src/nb_ndarray.cpp b/src/nb_ndarray.cpp
index 6cbb9e19..b8054c2c 100644
--- a/src/nb_ndarray.cpp
+++ b/src/nb_ndarray.cpp
@@ -293,6 +293,8 @@ static PyObject *dlpack_from_buffer_protocol(PyObject *o, bool ro) {
     }
 
     mt->deleter = [](managed_dltensor *mt2) {
+        if (!is_alive())
+            return;
         gil_scoped_acquire guard;
         Py_buffer *buf = (Py_buffer *) mt2->manager_ctx;
         PyBuffer_Release(buf);
@@ -617,7 +619,7 @@ void ndarray_dec_ref(ndarray_handle *th) noexcept {
 
     if (rc_value == 0) {
         check(false, "ndarray_dec_ref(): reference count became negative!");
-    } else if (rc_value == 1) {
+    } else if (rc_value == 1 && is_alive()) {
         gil_scoped_acquire guard;
 
         Py_XDECREF(th->owner);
@@ -662,6 +664,8 @@ ndarray_handle *ndarray_create(void *value, size_t ndim, const size_t *shape_in,
     scoped_pymalloc<int64_t> shape(ndim), strides(ndim);
 
     auto deleter = [](managed_dltensor *mt) {
+        if (!is_alive())
+            return;
         gil_scoped_acquire guard;
         ndarray_handle *th = (ndarray_handle *) mt->manager_ctx;
         ndarray_dec_ref(th);