In an introductory dream sequence, Charlie Carbone [Josh Keaton] and Louis Booker [Ahmed Best] film a shampoo commercial in Australia, directed by their kangaroo friend Jackie Legs [Jeff Bennett]. Louis believes the dream signals trouble for Jackie, but Charlie, Louis’s best friend, and Charlie's wife Jessie [Kath Soucie] treat it as mere fantasy. Back in Australia, they search for a local Aboriginal tribe to help them source sweet-smelling berries for their new line of shampoo. The tribe’s leader, Ankamuti [Obba Babatundé], reveals that his people have lost the source of their mystical power: four precious jewels. He hints that Charlie and Louis are the chosen ones who must find and return these gems.
While on the quest, the trio reunites with Jackie Legs and his family. A group of animal smugglers raides the area, Jackie is separated and captured. Charlie, Louis, and Jessie vow to rescue him and the other animals. They secretly sneak into the back of a truck, finding a tranquilized Jackie in a crate. When one of the smugglers checks the crate, Louis’s accidental pass of gas spooks them, and the three are hauled away in the confusion.
The next day, Charlie, Louis, and Jessie are shipped from Sydney to Las Vegas, where Jackie and the other animals are headed for Outback Ollie, a television show host and zookeeper. They end up in a warehouse in Las Vegas with the animals. After a daring break, they free Jackie, still unconscious, and escape in a golf cart. They cross paths with limousine driver Ronald Booker [Keith Diamond], Louis’s cousin, and hop into his limo to dodge further attention. Jackie hops out and darts toward other vehicles, triggering a traffic jam.
The group hides in an apartment building but are confronted by two cops who try to arrest them for jewel theft and animal smuggling. Louis attacks and knocks them out, exposing the deception. Ronald leaves them, and the trio continues the chase in his limo, damaging his vehicle in the process. Their pursuit leads them to Mrs. Sperling’s backyard, where they locate Jackie. He escapes again and heads toward a boating resort, with Charlie, Louis, Jessie, and the help of Outback Ollie closing in.
Ollie betrays them, promising to return Jackie to safety. The trio heads to Ollie’s zoo, where he plans to kill the captured animals. Charlie, Louis, Jessie, along with Ronald and the FBI, expose Ollie as a criminal. Ollie holds Jessie hostage, threatening her fate at the jaws of crocodiles, but Jackie rescues her. With the capture of Ollie and his henchmen, the gems are returned to Charlie, Louis, and Jessie.
A few days later, Jackie and the animals are returned to Australia. Charlie, Louis, and Jessie return to Ankamuti to present the gems, and in gratitude, Ankamuti grants them the ability to understand Jackie and the other animals’ speech. Jackie thanks them and proclaims that they are truly “friends for life.”
