diff --git a/Lib/test/test_ctypes/test_pointers.py b/Lib/test/test_ctypes/test_pointers.py
index 78480af34474a54..eb3a5fdaa188c1e 100644
--- a/Lib/test/test_ctypes/test_pointers.py
+++ b/Lib/test/test_ctypes/test_pointers.py
@@ -98,6 +98,19 @@ def test_change_pointers(self):
         x.value = -99
         self.assertEqual(res.contents.value, -99)
 
+    def test_contents_rejects_spoofed_class(self):
+        # gh-161390: __class__ must not make a non-ctypes object look valid.
+        class Forge:
+            __slots__ = ("a", "b", "c", "d")
+            __class__ = c_int
+
+            def __init__(self):
+                self.a = c_int(7)
+                self.b = self.c = self.d = None
+
+        with self.assertRaises(TypeError):
+            pointer(c_int(1)).contents = Forge()
+
     def test_callbacks_with_pointers(self):
         # a function type receiving a pointer
         PROTOTYPE = CFUNCTYPE(c_int, POINTER(c_int))
diff --git a/Misc/NEWS.d/next/Library/2026-11-05-15-20-00.gh-issue-161390.p8Kq2m.rst b/Misc/NEWS.d/next/Library/2026-11-05-15-20-00.gh-issue-161390.p8Kq2m.rst
new file mode 100644
index 000000000000000..d1f9c18253a5755
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2026-11-05-15-20-00.gh-issue-161390.p8Kq2m.rst
@@ -0,0 +1,4 @@
+Assigning to the ``contents`` attribute of a :mod:`ctypes` pointer now
+raises :exc:`TypeError` when the value is not a ctypes object. A value
+whose ``__class__`` claimed to be a ctypes type could previously crash
+the interpreter.
diff --git a/Modules/_ctypes/_ctypes.c b/Modules/_ctypes/_ctypes.c
index 56d39e29f140dd0..ce53a7a70ad7522 100644
--- a/Modules/_ctypes/_ctypes.c
+++ b/Modules/_ctypes/_ctypes.c
@@ -5785,16 +5785,12 @@ Pointer_set_contents_lock_held(PyObject *op, PyObject *value, void *closure)
     assert(stginfo); /* Cannot be NULL for pointer instances */
     assert(stginfo->proto);
     if (!CDataObject_Check(st, value)) {
-        int res = PyObject_IsInstance(value, stginfo->proto);
-        if (res == -1)
-            return -1;
-        if (!res) {
-            PyErr_Format(PyExc_TypeError,
-                         "expected %s instead of %s",
-                         ((PyTypeObject *)(stginfo->proto))->tp_name,
-                         Py_TYPE(value)->tp_name);
-            return -1;
-        }
+        /* PyObject_IsInstance() follows a spoofed __class__ (gh-161390). */
+        PyErr_Format(PyExc_TypeError,
+                     "expected %s instead of %s",
+                     ((PyTypeObject *)(stginfo->proto))->tp_name,
+                     Py_TYPE(value)->tp_name);
+        return -1;
     }
 
     dst = (CDataObject *)value;