diff --git a/Lib/base64.py b/Lib/base64.py
index 36688ce43917ce..dcfcbcc95a39be 100644
--- a/Lib/base64.py
+++ b/Lib/base64.py
@@ -100,7 +100,13 @@ def b64decode(s, altchars=None, validate=_NOT_SPECIFIED, *, ignorechars=_NOT_SPE
                     break
             s = s.translate(bytes.maketrans(altchars, b'+/'))
         else:
-            trans = bytes.maketrans(b'+/' + altchars, altchars + b'+/')
+            trans_in = set(b'+/') - set(altchars)
+            if len(trans_in) == 2:
+                # we can't use the reqult of unordered sets here
+                trans = bytes.maketrans(altchars + b'+/', b'+/' + altchars)
+            else:
+                trans = bytes.maketrans(altchars + bytes(trans_in),
+                                        b'+/' + bytes(set(altchars) - set(b'+/')))
             s = s.translate(trans)
             ignorechars = ignorechars.translate(trans)
     if ignorechars is _NOT_SPECIFIED:
diff --git a/Lib/test/test_base64.py b/Lib/test/test_base64.py
index 69aa628db7c34c..9648624b267a54 100644
--- a/Lib/test/test_base64.py
+++ b/Lib/test/test_base64.py
@@ -293,6 +293,13 @@ def test_b64decode_altchars(self):
             eq(base64.b64decode(data_str, altchars=altchars_str), res)
             eq(base64.b64decode(data, altchars=altchars, ignorechars=b'\n'), res)
 
+        eq(base64.b64decode(b'/----', altchars=b'-+', ignorechars=b'/'), b'\xfb\xef\xbe')
+        eq(base64.b64decode(b'/----', altchars=b'+-', ignorechars=b'/'), b'\xff\xff\xff')
+        eq(base64.b64decode(b'+----', altchars=b'-/', ignorechars=b'+'), b'\xfb\xef\xbe')
+        eq(base64.b64decode(b'+----', altchars=b'/-', ignorechars=b'+'), b'\xff\xff\xff')
+        eq(base64.b64decode(b'+/+/', altchars=b'/+', ignorechars=b''), b'\xff\xef\xfe')
+        eq(base64.b64decode(b'/+/+', altchars=b'+/', ignorechars=b''), b'\xff\xef\xfe')
+
         self.assertRaises(ValueError, base64.b64decode, b'', altchars=b'+')
         self.assertRaises(ValueError, base64.b64decode, b'', altchars=b'+/-')
         self.assertRaises(ValueError, base64.b64decode, '', altchars='+')
diff --git a/Misc/NEWS.d/next/Library/2026-03-15-10-17-51.gh-issue-145968.gZexry.rst b/Misc/NEWS.d/next/Library/2026-03-15-10-17-51.gh-issue-145968.gZexry.rst
new file mode 100644
index 00000000000000..9eae1dc400838a
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2026-03-15-10-17-51.gh-issue-145968.gZexry.rst
@@ -0,0 +1,2 @@
+Fix translation in :func:`base64.b64decode` when altchars overlaps with the
+standard ones.