Marmaduke (Owen Wilson) is a Great Dane, living in rural Kansas with his best friend who is a cat named Carlos (George Lopez). His owner, Phil (Lee Pace), works as a marketing director for a dog food company. Phil is very strict with Marmaduke. His wife is Debbie (Judy Greer) and they have three children, Brian (Finley Jacobsen), Barbara (Caroline Sunshine) and Sarah (Milana Haines).