diff --git a/Lib/pdb.py b/Lib/pdb.py
index f89d104fcddb9a..cbe7b30b52fd22 100644
--- a/Lib/pdb.py
+++ b/Lib/pdb.py
@@ -762,9 +762,32 @@ def input_auto_indent():
                     # If the last line is empty, we don't need to indent
                     return
 
+                # A stack to keep track of string delimiters (quotes). Push a
+                # quote when entering a string, and pop it when the string
+                # ends. When the stack is empty, we're not inside a string. If
+                # encounter a '#' while not inside a string, it's a comment
+                # start; otherwise, it's just a '#' character within a string.
+                in_string: list[str] = []
+                last_char = None
                 last_line = last_line.rstrip('\r\n')
                 indent = len(last_line) - len(last_line.lstrip())
-                if last_line.endswith(":"):
+
+                for i, char in enumerate(last_line):
+                    if char == "#":
+                        if in_string:
+                            last_char = char # hashtag in string, not comment
+                        else:
+                            break # ignore from comment start to line end
+                    elif char not in " \t" and not in_string:
+                        last_char = char
+
+                    if char in "\"'" and (i == 0 or last_line[i - 1] != "\\"):
+                        if in_string and in_string[-1] == char:
+                            in_string.pop()
+                        else:
+                            in_string.append(char)
+
+                if last_char == ":":
                     indent += 4
                 readline.insert_text(' ' * indent)
 
diff --git a/Lib/test/test_pdb.py b/Lib/test/test_pdb.py
index 68c2b508fa64dc..00c35dd0f6614e 100644
--- a/Lib/test/test_pdb.py
+++ b/Lib/test/test_pdb.py
@@ -4870,6 +4870,22 @@ def test_multiline_auto_indent(self):
 
         self.assertIn(b'42', output)
 
+        # can ignore comment to locate trailing colon
+        input = b"def f(s): # comment\n"
+        # can distinguish hashtag from comment
+        input += b"if s == '#':\n"
+        input += b"return 's == ' + '#'\n"
+        # can ignore all comments, not just from the rightmost '#' to end
+        input += b"\x08\x08\x08\x08else: ##\n"
+        input += b"return 's != ' + '#'\n"
+        input += b"\n"
+        input += b"f('#')\n"
+        input += b"c\n"
+
+        output = run_pty(script, input)
+
+        self.assertIn(b's == #', output)
+
     def test_multiline_completion(self):
         script = textwrap.dedent("""
             import pdb; pdb.Pdb().set_trace()
diff --git a/Misc/NEWS.d/next/Library/2025-05-09-03-00-41.gh-issue-133698.xeJehW.rst b/Misc/NEWS.d/next/Library/2025-05-09-03-00-41.gh-issue-133698.xeJehW.rst
new file mode 100644
index 00000000000000..42a3cc1cd566eb
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2025-05-09-03-00-41.gh-issue-133698.xeJehW.rst
@@ -0,0 +1 @@
+Fix :mod:`pdb` multiline auto-indent not work with comments.