Live-action actors
- Judy Greer as Debbie Winslow
- Lee Pace as Phil Winslow
- William H. Macy as Don Twombly
- Finley Jacobsen as Billy Winslow
- Caroline Sunshine as Barbara Winslow
- Michael Teigen as Gray
]Voice actors
- Owen Wilson as Marmaduke: a Great Dane and the protagonist.
- George Lopez as Carlos: a Balinese who is annoyed by Marmaduke.
- Fergie as Jezebel: a Rough Collie (or possibly a Shetland Sheepdog) who likes Marmaduke and has a crush on him.
- Kiefer Sutherland as Bosco: a Beauceron and the main antagonist.
- Emma Stone as Mazie: an energetic Australian Shepherd who loves to roll around.
- Christopher Mintz-Plasse as Giuseppe: a stylized Chinese Crested.
- Sam Elliott as Chupadogra
- Steve Coogan as Raisin
- David Walliams as Anton Harrison
- Marlon Wayans as Lightning
- Thomas F. Wilson (as Tom Wilson)
- Devon Werkheiser as Drama Dog
- Ryan Devlin as Deuce (voice)
- Jennifer Louise La Voie as Teacup Poodle
- Damon Wayans, Jr. as Thunder
- Brad Williams as Beagle (uncredited
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