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- Lacey Chabert as Elizabeth "Eliza" Thornberry, an adventurous 12-year-old-girl who possesses the power to communicate with animals.
- Tom Kane as Darwin Thornberry, a chimpanzee and Eliza's best friend.
- Flea as Donald Michael "Donnie" Thornberry, Debbie and Eliza's feral, adopted 5-year-old brother.
- Danielle Harris as Deborah "Debbie" Thornberry, Eliza's 16-year-old sister.
- Tim Curry as Nigel Thornberry, Eliza's dad who runs a nature television show.
- Jodi Carlisle as Marianne Thornberry, Nigel's American-born wife and the director/camera operator, as well as Eliza's mom.
- Cree Summer as Phaedra, the female elephant who is Eliza's best friend. She also returned from the First movie.
- Whoopi Goldberg as Ellie, a female elephant who is Phaedra's mother.
- This is a sequel to The Wild Thornberrys Movie (2002).
- Eliza go swimming with Phaedra and Ellie at the watering hole.
- Eliza wears a blue bathing suit and see her buttocks for swimming at the watering hole.
- Eliza also wears her blue bathing suit with brown shorts.
- Eliza and Darwin also rides on Phaedra's back while swimming at the watering hole.
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