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|Penélope Cruz||Juarez the Guinea Pig (voice)|
|Tracy Morgan||Blaster the Guinea Pig (voice)|
|Jon Favreau||Hurley the Guinea Pig (voice)|
|Steve Buscemi||Bucky the Hamster (voice)|
|Nicolas Cage||Speckles the Mole (voice)|
|Edwin Louis||Mooch the Fly (voice)|
|Jared Lavette||Jared the Skunk (voice)|
|Micah Lavette||Micah the Fox (voice)|
|Bill Nighy||Leonard Saber|
|Will Arnett||Kip Killian|
|Loudon Wainwright III||Grandpa Goodman|
|Tyler Patrick Jones||Connor|
|Piper Mackenzie Harris||Penny|
|Chris Ellis||NSA Director|
|Dee Bradley Baker|
|Sam Rockwell||Darwin the Guinea Pig (voice)|
|Michael Papajohn||FBI Techie|
|Hoyt Yeatman||Story Contributor|
|M. Scott Smith||Editing|
|Bud S. Smith||Editing|
"The world needs bigger heroes"
The film revolves around a special team of trained secret agent animals, equipped with advanced tools that allows the mammalian members to talk to humans. The primary field team consists of Darwin (team leader), Juarez (martial arts), Blaster (weapons/transportation), star-nosed mole Speckles (cyber intelligence), and fly Mooch (reconnaissance). The unit's leader Ben, orders an unauthorised infiltration of the residence of home electronics and appliances magnates, Leonard Saber, the owner of Saberling Technology, who has been under FBI investigation. The team is able to retrieve sensitive information about a sinister scheme that is set to occur in 29 hours. However, when Ben's superior arrives for his evaluation, his astonishment at the team's capabilities and technology is overcome by his indignation at Ben's unauthorized mission and the fact that the downloaded intelligence appears to be useless information about Saber's coffee makers. As a result, the government agent orders the unit shut down, the equipment seized and the animals to be used as experimental subjects to be killed. With the help of their human compatriots, Darwin, Juarez, Blaster, Mooch, and Speckles escape with hopes of stopping Saber's scheme, but find themselves in a pet carrying case bound for a pet shop.
Trapped in the store's pet rodent display case, G-Force meets Hurley, Bucky, an irascible hamster and three sycophantic mice. Although Blaster and Juarez manage to get themselves sold to a family with plans to return to extract their comrades, Speckles' own attempt to escape by playing dead ends disastrously when he is thrown into and supposedly crushed in a garbage truck. Meanwhile, Mooch manages to return to Ben to tell him where his mammalian agents are, but Darwin escapes with Hurley before he can arrive to collect them.
While Blaster and Juarez escape their new owners to return to Ben, he and his partner discover that the discredited intel has a destructive computer function that apparently hid the scheme. At this time, Darwin and Hurley make their own way to their superior. En route, Darwin sees a Saber coffee maker and decides to investigate it, but his examination of the machine makes it come alive as a dangerous fighting robot that he and Hurley are able to defeat. Later Darwin and Hurley transport the wreckage to Ben by a skateboard. However, upon arrival, Ben confesses the shattering information that they are not special genetically enhanced animals as previously told, but ordinary ones Ben took in and trained for the team (Juarez has a delicacy in an unknown location, Blaster was found at a hair and cosmetics place where a hair gel was being tested, Speckles was found before his home was destroyed by humans, and Darwin's parents abandoned him because he was the runt of the litter). However, Hurley lifts them from their despair by reminding the team of the astounding feats he has seen them do and the fact that they obviously made themselves extraordinary on their own.
Emboldened but with little time to stop the scheme, Ben provides the field team with the means to infiltrate the Saber residence and plant a virus in the computer mainframe. Unfortunately, FBI agents are ordered to capture the animals dead or alive, forcing the team to elude them with an extended pursuit thanks to a high speed vehicle especially designed for them called the Rapid Deployment Vehicle (dubbed the RDV by Darwin). After that is accomplished and the team infiltrates Saber's mainframe, the plan is put into motion, and the resulting battle separates the group, only leaving Darwin and Mooch to take the mainframe down. At the same time, Leonard Saber is shocked to discover that his appliances have become killing machines, expecting them to simply be able to effectively communicate with each other, while FBI takes advantage of this obvious pretext to finally openly move against the industrialist. When Darwin reaches the mainframe, he finds out that Speckles is the mastermind of the plan, whose masterstroke is to cause a massive planetwide bombardment of space junk pulled from orbit to make the planet surface uninhabitable. Speckles promptly amalgamates the various appliances in the vicinity into a giant walking robot like being, which, combined with a localised bombardment of orbital debris, soon overpowers the police forces gathered at the mansion. Darwin manages to persuade Speckles that his new family is with the rest of the team and Ben, who had taken them all in. Speckles concedes, and realising that he has gone too far, tries to shut it down, but he has lost control and the machines continue their onslaught. Darwin uses the computer virus on his PDA to take it down.
The guinea pigs are personally commended by the FBI Director who also appoints them special agents of the FBI. Furthermore, G-Force is reinstated as a unit of the Bureau and expanded with Hurley, Bucky and the mice inducted as new recruits. Meanwhile, Saber makes the largest product recall in history, Speckles is given the punitive duty of personally removing the malicious chips from all Saber products, which number into the tens of millions, and Agent Killian was relocated to an FBI base in the South Pole.