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| Bruce Willis | Spike the Dog |
| Chrissie Hynde | Siri the Leopard |
| Nancy Cartwright | Chuckie Finster |
| Kath Soucie | Betty DeVille/Lil DeVille/Phil DeVille |
| Cheryl Chase | Angelica Pickles |
| Tara Strong | Dil Pickles |
| Melanie Chartoff | Didi Pickles |
| Jack Riley | Stu Pickles |
| Tress MacNeille | Charlotte Pickles |
| Michael Bell | Drew Pickles / Chas Finster |
| Dionne Quan | Kimi |
| Cree Summer | Susie Carmichael |
| Lacey Chabert | Eliza Thornberry |
| Tim Curry | Sir Nigel Thornberry |
| Danielle Harris | Debbie Thornberry |
| Tom Kane | Darwin |
| Jodi Carlisle | Marianne Thornberry |
| Elizabeth Daily | Tommy Pickles |
| Flea | Donnie Thornberry |
The toddlers meet the Thornberry family after an accident leaves them stranded on a tropical island.
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