Dakota Fanning as Sally (The Cat in the Hat (2003)) as Carmen Walden, Joan's dull, well-behaved, and rule-obeying daughter and the main protagonist.
Spencer Breslin as Conrad (The Cat in the Hat (2003)) as Conrad Walden, Joan's destructive and misbehaved son and Carmen's husband. He's the tritagonist
Mike Myers as the Cat in the Hat (The Cat in the Hat (2003)) as Phil, a giant, anthropomorphic, wise-cracking cat with a Brooklyn accent and the duetergonist.
Alec Baldwin as Lawrence "Larry" Quinn (The Cat in the Hat (2003)) as Larry Quinn, the Waldens' pompous, lazy, unemployed next-door neighbor. He is allergic to cats, and is determined to both marry Joan for her wealth and send Conrad to military school to straighten up his behavior.
Amy Hill as Mrs. Kwan, an elderly Asian woman with a thick Japanese accent that gets hired to watch the kids, though she sleeps through her job. Her weight and sleep serves as a running gag.
Sean Hayes as Mr. Humberfloob, Joan's employer. He is also the voice of the family Fish.
Jim Cummings as Thing One (The Cat in the Hat (2003)) as Thing 1 and Matt Lucas as Thing Two (The Cat in the Hat (2003)) as Thing 2; two gibbering trouble-making creatures that Phil brings in with him. Robin Williams provided the voices for both Things.
Bugsy as Nevins, the Waldens' pet dog. Frank Welker provided his voice.