James Marsden as Diggs (voice)

Nick Nolte as Butch (voice)

Christina Applegate as Catherine (voice)

Bette Midler as Kitty Galore (voice)

Pascale Hutton as Jackie

Katt Williams as Seamus (voice)

Neil Patrick Harris as Lou (voice)

Sean Hayes as Mr. Tinkles (voice)

Wallace Shawn as Calico (voice)

Roger Moore as Tab Lazenby (voice)

Joe Pantoliano as Peek (voice)

Michael Clarke Duncan as Sam (voice)

Chris O'Donnell as Shane

Jack McBrayer as Chuck

Fred Armisen as Freidrich

Kiernan Shipka as Little Girl

Paul Rodríguez as Crazy Carlito (voice)

J.K. Simmons as Gruff K-9 (voice)

Grey DeLisle as Security Bulldog/Catherine's Niece/Cat Spy Analyst

E. G. Daily as Scrumptious / Patches / Catherine's Niece (voice)

Phil LaMarr as Paws / Cat Spy Analyst (voice)

Michael Beattie as Angus MacDougall (voice)

Jeff Bennett as Duncan MacDougall (voice)

Malcolm Stewart as Captain Flemming

Dawn Chubai as Reporter

Keith Dallas as Coit Tower Guard

Len Morganti as Rex (voice)

Betty Phillips as Cat Lady

Christopher Lee Parson as Hep Cat / Cat Spy Analyst (voice)

Bumper Robinson as Cool Cat / Dog Killa / Cat Spy Analyst / Slim (voice)

Rick D. Wasserman as Rocky (voice)

Roger L. Jackson as Inmate Fat Cat (voice)

Bonnie Cahoon as Dog HQ PA / Catherine's Niece (voice)

André Sogliuzzo as Snobby K-9 (voice)

Carlos Alazraqui as Cat Gunner / Cat Spy Analyst (voice)

Grey DeLisle as Security Bulldog / Catherine's Niece / Cat Spy Analyst (voice)

Ingrid Tesch as Mom

Amitai Marmorstein as Playland Worker

Robert Hewko as Old Man

Mark Burgess as Used Car Salesman

Sage Brocklebank as Park Patron