In an ensemble cast, Cameron Diaz, Drew Barrymore and Lucy Liu return as Natalie, Dylan, and Alex respectively. It also features Demi Moore, Shia LaBeouf, Robert Patrick, Crispin Glover, Justin Theroux, Matt LeBlanc, Luke Wilson, John Cleese, and replacing Bill Murray in the role of Bosley, Bernie Mac.
Plot
After Rescuing US Marshal Ray Carter (Robert Patrick) in Mongolia, the Angels, Natalie (Cameron Diaz), Dylan (Drew Barrymore), and Alex (Lucy Liu) are hired to locate a set of titanium rings called H.A.L.O. (Hidden Alias List Operation) stolen from the Department of Justice that, when put together in a machine, will display a list of all individuals in the witness protection program, Justice Department official William Rose Bailey (Bruce Willis), who possessed one of the rings, was murdered in the process. Having discovered that one of the protected witnesses, Alan Caulfield (Eric Bogosian) was murdered in his house in San Bernardino, the Angels investigate the scene and discover evidence suggesting that Caulfield was smothered with a bag and the killer is a surfer with a scar on his left leg. Meanwhile, Natalie and her now boyfriend Peter Kominsky (Luke Wilson) are moving in together, with some help from Alex's boyfriend Jason Gibbons (Matt LeBlanc), who's relationship with Alex is on a "time out".
Later, Alex reunites with her father (John Cleese), who is unaware of Alex's job at the agency. While undercover at a local beach, Alex asks Dylan who would be the first of them to leave the agency, since Natalie and Peter moved in together and might get married soon. Later, the Angels head to a motorcycle competition called the Coal Bowl, were the killer, Randy Emmers (Rodrigo Santoro) targets Max Petroni (Shia LaBeouf), who is subsequently sent to Mama Bosley's (Ja'net Dubois) house for protection. during the race, the Thin Man (Crispin Glover) kills Emmers by stabbing him with a shoe knife. the Angels find photos of Alan Caulfield and Max Petroni in Emmers coat pocket, and to their astonishment find a photo of Dylan as well. Dylan reveals to the Angels that she was born Helen Zaas and is in the program herself for sending her ex-boyfriend Seamus O'Grady (Justin Theroux), the leader of the O'Grady Mob, to prison. Max also reveals that the O'Gradys murdered his parents, and he later testified against them. Natalie realizes that Alan Caulfield also testified against the O'Gradys and that they have the H.A.L.O. rings. Also, the Angels go undercover as nuns at a prep school were they learn of the Thin Man's past from the mother superior (Carrie Fisher).
The Angels then find the rings at the San Pedro Harbour. Dylan then sees Seamus, whom she hasn't seen in eight years. The Angels engage in a fist fight with Seamus and the O'Grady Mob. Meanwhile, Natalie attends Peter's high school reunion in Hermosa Beach, also, Jason tells Alex's father of her job at the agency. Alex apologizes for not telling him the truth, but he forgives her, declaring that whatever makes her happy, he will support it. Later, Dylan leaves the Angels because she doesn't want to endanger them with Seamus' vendetta, but a vision of former Angel Kelly Garrett (Jaclyn Smith) at a bar in Mexico prompts her to return. Just as Ray Carter retrieves the rings, Bosley passes his car keys and Carter reaches for them. Carter passes them back, claiming that their not his. Natalie and Alex realize that Carter is in on the scheme and faked his injury so he wouldn't be considered a suspect. The Angels deduce that former angel Madison Lee (Demi Moore), who had just killed Carter, is the perpetrator of the crimes due to her being the only individual possessing the necessary contacts to carry out such a scheme. Madison shoots the Angels and reacquires the rings, however, the Angels were wearing Kevlar vests that saved them.
Madison returns to the agency to "confront" Charlie, rejecting his attempts to remind her that the Angels are a family and shooting his speaker off the desk, coldly sneering that she wasn't just a good Angel, but was the best, rejecting the idea that she ever needed her teammates. Learning that the rings will be sold after a rendezvous on the Hollywood Walk of Fame, the Angels travel to Los Angeles. They set the Antonioni Crime Family, the Tanaka Yakuza, and the Diablo Cartel up to be caught by the FBI in a faked rendezvous. With Madison having contacted the O'Gradys to act as security, Alex and Dylan take out the O'Gradys, while Natalie and Madison go head-to-head themselves. Seamus kills the Thin Man as he shares a kiss with Dylan and Seamus and Dylan fight, but when Seamus was about to burn her with his lighter, she gets a chance to kick Seamus off the building and he falls to his death, with the Angels subsequently stopping Madison's attempt to blow up the premiere of Alex's boyfriend Jason's new movie thanks to Bosley knocking the bomb away. Although Madison tries to escape, the Angels defeat her in a final confrontation at an abandoned theatre, throwing her through a gas main just as she fires her gun, causing an explosion that kills her.
At the movie premiere, it is revealed that Mama Bosley adopted Max, Peter bought a puppy for Natalie they named Spike, Jason's "time out" with Alex is over and they share a kiss, despite living together, Natalie says she will stay with the agency no matter what, and the Angels celebrate their victory.
