diff --git a/Lib/ctypes/_endian.py b/Lib/ctypes/_endian.py
index 34dee64b1a65a6..6f674b21371c40 100644
--- a/Lib/ctypes/_endian.py
+++ b/Lib/ctypes/_endian.py
@@ -15,8 +15,8 @@ def _other_endian(typ):
     # if typ is array
     if isinstance(typ, _array_type):
         return _other_endian(typ._type_) * typ._length_
-    # if typ is structure
-    if issubclass(typ, Structure):
+    # if typ is structure or union
+    if issubclass(typ, (Structure, Union)):
         return typ
     raise TypeError("This type does not support other endian: %s" % typ)
 
diff --git a/Lib/ctypes/test/test_byteswap.py b/Lib/ctypes/test/test_byteswap.py
index caefb774cc5375..44d32ff27ba923 100644
--- a/Lib/ctypes/test/test_byteswap.py
+++ b/Lib/ctypes/test/test_byteswap.py
@@ -352,5 +352,24 @@ class TestUnion(parent):
                 self.assertEqual(s.point.x, 1)
                 self.assertEqual(s.point.y, 2)
 
+    def test_build_struct_union_opposite_system_byteorder(self):
+        # gh-105102
+        if sys.byteorder == "little":
+            _Structure = BigEndianStructure
+            _Union = BigEndianUnion
+        else:
+            _Structure = LittleEndianStructure
+            _Union = LittleEndianUnion
+
+        class S1(_Structure):
+            _fields_ = [("a", c_byte), ("b", c_byte)]
+
+        class U1(_Union):
+            _fields_ = [("s1", S1), ("ab", c_short)]
+
+        class S2(_Structure):
+            _fields_ = [("u1", U1), ("c", c_byte)]
+
+
 if __name__ == "__main__":
     unittest.main()
diff --git a/Misc/NEWS.d/next/Library/2023-05-30-18-30-11.gh-issue-105102.SnpK04.rst b/Misc/NEWS.d/next/Library/2023-05-30-18-30-11.gh-issue-105102.SnpK04.rst
new file mode 100644
index 00000000000000..7ca21afefa3132
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2023-05-30-18-30-11.gh-issue-105102.SnpK04.rst
@@ -0,0 +1,2 @@
+Allow :class:`ctypes.Union` to be nested in :class:`ctypes.Structure` when
+the system endianness is the opposite of the classes.