diff --git a/Lib/base64.py b/Lib/base64.py
index 5d78cc09f40cd3..edac542a7dca4c 100644
--- a/Lib/base64.py
+++ b/Lib/base64.py
@@ -78,11 +78,27 @@ def b64decode(s, altchars=None, validate=False):
     https://docs.python.org/3.11/library/binascii.html#binascii.a2b_base64
     """
     s = _bytes_from_decode_data(s)
+    badchar = None
     if altchars is not None:
         altchars = _bytes_from_decode_data(altchars)
-        assert len(altchars) == 2, repr(altchars)
-        s = s.translate(bytes.maketrans(altchars, b'+/'))
-    return binascii.a2b_base64(s, strict_mode=validate)
+        if len(altchars) != 2:
+            raise ValueError(f'invalid altchars: {altchars!r}')
+        if validate:
+            s = s.translate(bytes.maketrans(b'+/' + altchars, altchars + b'+/'))
+        else:
+            for b in set(b'+/') - set(altchars):
+                if b in s:
+                    badchar = b
+                    break
+            s = s.translate(bytes.maketrans(altchars, b'+/'))
+    result = binascii.a2b_base64(s, strict_mode=validate)
+    if badchar is not None:
+        import warnings
+        warnings.warn(f'invalid character {chr(badchar)!a} in base64 data '
+                      f'with altchars={altchars!r} will be discarded in '
+                      f'future Python versions',
+                      FutureWarning, stacklevel=2)
+    return result
 
 
 def standard_b64encode(s):
@@ -104,7 +120,7 @@ def standard_b64decode(s):
 
 
 _urlsafe_encode_translation = bytes.maketrans(b'+/', b'-_')
-_urlsafe_decode_translation = bytes.maketrans(b'-_', b'+/')
+_urlsafe_decode_translation = bytes.maketrans(b'+/-_', b'-_+/')
 
 def urlsafe_b64encode(s):
     """Encode bytes using the URL- and filesystem-safe Base64 alphabet.
diff --git a/Lib/test/test_base64.py b/Lib/test/test_base64.py
index ac3f09405457df..312db0f3a0f776 100644
--- a/Lib/test/test_base64.py
+++ b/Lib/test/test_base64.py
@@ -265,6 +265,11 @@ def test_b64decode_altchars(self):
             eq(base64.b64decode(data, altchars=altchars_str), res)
             eq(base64.b64decode(data_str, altchars=altchars_str), res)
 
+        self.assertRaises(ValueError, base64.b64decode, b'', altchars=b'+')
+        self.assertRaises(ValueError, base64.b64decode, b'', altchars=b'+/-')
+        self.assertRaises(ValueError, base64.b64decode, '', altchars='+')
+        self.assertRaises(ValueError, base64.b64decode, '', altchars='+/-')
+
     def test_b64decode_padding_error(self):
         self.assertRaises(binascii.Error, base64.b64decode, b'abc')
         self.assertRaises(binascii.Error, base64.b64decode, 'abc')
@@ -296,13 +301,21 @@ def test_b64decode_invalid_chars(self):
             with self.assertRaises(binascii.Error):
                 base64.b64decode(bstr.decode('ascii'), validate=True)
 
-        # Normal alphabet characters not discarded when alternative given
-        res = b'\xfb\xef\xff'
-        self.assertEqual(base64.b64decode(b'++//', validate=True), res)
-        self.assertEqual(base64.b64decode(b'++//', '-_', validate=True), res)
-        self.assertEqual(base64.b64decode(b'--__', '-_', validate=True), res)
-        self.assertEqual(base64.urlsafe_b64decode(b'++//'), res)
-        self.assertEqual(base64.urlsafe_b64decode(b'--__'), res)
+        # Normal alphabet characters will be discarded when alternative given
+        with self.assertWarns(FutureWarning):
+            self.assertEqual(base64.b64decode(b'++++', altchars=b'-_'),
+                             b'\xfb\xef\xbe')
+        with self.assertWarns(FutureWarning):
+            self.assertEqual(base64.b64decode(b'////', altchars=b'-_'),
+                             b'\xff\xff\xff')
+        self.assertEqual(base64.urlsafe_b64decode(b'++++'), b'')
+        self.assertEqual(base64.urlsafe_b64decode(b'////'), b'')
+        with self.assertRaises(binascii.Error):
+            base64.b64decode(b'++++', altchars=b'-_', validate=True)
+        with self.assertRaises(binascii.Error):
+            base64.b64decode(b'////', altchars=b'-_', validate=True)
+        with self.assertRaises(binascii.Error):
+            base64.b64decode(b'+/!', altchars=b'-_')
 
     def _altchars_strategy():
         """Generate 'altchars' for base64 encoding."""
diff --git a/Misc/NEWS.d/next/Security/2025-11-06-12-03-29.gh-issue-125346.7Gfpgw.rst b/Misc/NEWS.d/next/Security/2025-11-06-12-03-29.gh-issue-125346.7Gfpgw.rst
new file mode 100644
index 00000000000000..6fec18992622d5
--- /dev/null
+++ b/Misc/NEWS.d/next/Security/2025-11-06-12-03-29.gh-issue-125346.7Gfpgw.rst
@@ -0,0 +1,4 @@
+The ``+`` and ``/`` characters are no longer recognized as the part of the
+Base64 alphabet in :func:`base64.urlsafe_b64decode` and
+:func:`base64.b64decode` with the *altchars* argument that does not contain
+them.