Natalie Cook, Dylan Sanders, and Alex Munday are the "Angels", three women who work as private investigators together for unseen millionaire Charlie Townsend. Charlie uses speakers in his offices to communicate with the Angels, and his assistant Bosley works with them directly when needed.
Charlie assigns the Angels to find Eric Knox, a software genius who created a revolutionary voice-recognition system and heads his own company, Knox Enterprises. He is believed to have been kidnapped by Roger Corwin, who runs the communications-satellite company Redstar.
The Angels infiltrate a party held by Corwin, spotting a suspicious-looking man that they had previously seen from surveillance videos of Knox's kidnapping. Dubbing him the "Thin Man", the Angels chase him down and fight him; he gets away, but the Angels find Knox, safely tied up nearby.
After the Angels reunite Knox with his business partner Vivian Wood, Charlie explains that they must determine whether the Thin Man has stolen Knox's voice-recognition software. The Angels infiltrate Redstar headquarters, fool the security system, and plant a device in the central computer to enable them to explore it remotely. They retire for the night after giving Bosley the laptop computer that communicates with the Redstar computer.
Dylan takes up Knox's offer to spend the night with him, and they end up having sex. Afterwards, he betrays her; simultaneously, attacks are made on Natalie and Alex, Bosley is captured by Vivian, and Corwin is murdered by the Thin Man. Knox tells Dylan his kidnapping was faked to get the Angels to help him access the Redstar satellite network. He plans to use it along with his voice recognition software to find and kill Charlie, who Knox asserts killed his father in the Vietnam War.
Dylan escapes and reunites with Natalie and Alex, who also survived their attacks. They approach Charlie's office just as the building explodes. They find a radio receiver that Bosley is able to communicate through via a tooth implanted radio transmitter. He provides enough information of where he is being held captive to allow Natalie to deduce his location, an abandoned lighthouse. With help from Dylan's friend Chad, the Angels stealthily approach by boat. Upon finding Knox, Dylan is captured by his henchmen, tied up and gagged.
The Angels are too late to stop Knox from determining Charlie's location, though they rescue Bosley while Dylan fights off her captors. They come together to defeat Vivian, the Thin Man, and other assorted henchmen, but Knox blows up the lighthouse and flies off in an attack helicopter towards Charlie's house. Bosley helps the Angels board it, where Alex reprograms the missile to have it shoot backwards; blowing up the helicopter and killing Knox while the Angels land safely.
Seeing the opportunity to finally meet Charlie in person, the Angels enter the nearby beach house that Knox had targeted, but he has already left. He remotely congratulates them on a job well done through another speaker, and treats them and Bosley to a vacation. Charlie also tells them that Knox's father was an undercover double agent; he was discovered and killed by the enemy, but not by him.
When he speaks to the Angels by telephone on the beach, they ask if they could ever meet him in person. Dylan suspects she sees him nearby talking into a cell phone, but does not tell the group; opting to raise a toast to Charlie instead. Bosley playfully douses the Angels with his drink, and they chase him towards the ocean. From afar, a silhouetted Charlie watches them and walks off.
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