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| Julia Roberts | Charlotte |
| Dakota Fanning | Fern |
| Steve Buscemi | Templeton |
| John Cleese | Samuel |
| Oprah Winfrey | Gussy |
| Cedric the Entertainer | Golly |
| Kathy Bates | Bitsy |
| Reba McEntire | Betsy |
| Robert Redford | Ike |
| Thomas Haden Church | Brooks |
| Dominic Scott Kay | Wilbur |
| André Benjamin | Elwyn |
| Kevin Anderson | Mr. Arable |
| Gary Basaraba | Mr. Zuckerman |
| Beau Bridges | Dr. Dorian |
| Essie Davis | Mrs. Arable |
| Siobhan Fallon Hogan | Mrs. Zuckerman |
| Sam Shepard | Narrator |
After learning that a young pig's days are numbered, a literate spider weaves an elaborate plan to save her friend from the butcher's block.
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