Four female students are about to graduate from a secret paramilitary academy known as D.E.B.S. (Discipline, Energy, Beauty, and Strength). The team consists of Max Brewer, who tends to draw her gun at the slightest provocation; Janet, who wishes for nothing but to earn her stripes as a true D.E.B.; the chain-smoking and promiscuous Dominique; and Amy Bradshaw, who is doubtful about being a spy, despite being an honor student at the academy. Amy has broken up with her boyfriend Bobby Matthews, a Homeland Security agent. Her personal life takes a back seat to the re-emergence of Lucy Diamond, a criminal mastermind who, by coincidence, is the subject of Amy's thesis. The D.E.B.S. are sent by the heads of D.E.B.S., Miss. Petrie and Mr. Phipps, to survey Lucy, expecting to witness criminal dealings, and unaware that Lucy has simply been set up on a blind date by her chief henchman and best friend, Scud to meet Russian assassin Ninotchka Kaprova.
The date is a complete disaster, ending in a shootout where Lucy escapes in the chaos. As the D.E.B.S. follow her, they split up, with Amy eventually running into Lucy. Lucy attempts to charm Amy, who is surprised to learn Lucy is a lesbian, since none of the material she studied for her thesis reveals this, into lowering her gun and disappears the moment Amy's attention wavers. The team is reunited, and they praise Amy for being the only federal agent who has ever encountered Lucy and lived to tell about it. Later, Lucy returns to speak with Amy and coerces her into going out for a night of fun, roping Janet into the events to prevent being found. They end up at a club, where Janet ends up bonding with Scud while Lucy further charms Amy. The two learn more about each other, and as Lucy senses Amy's attraction, she leans in to kiss her, only to be interrupted by a shocked Janet. Lucy takes the two D.E.B.S. home. Janet is indignant, claiming that Amy is violating protocol, and is further troubled at learning Amy might not be straight. Amy blackmails her into silence by telling her that she can withhold her stripes if she tells anybody.
The next day, Miss Petrie meets with Amy and promotes her to squad leader, effectively replacing Max. Max is furious, but must follow Amy as they respond to a bank heist orchestrated by Lucy. Amy and Max continue to bicker when responding to the bank heist, while unbeknownst to them, Lucy has only committed the crime in order to see Amy again. Amy finds Lucy, they kiss, and Lucy asks Amy to come with her. The other D.E.B.S. find a note spray-painted on the wall reading "I have the girl", that leads them to assume Amy has been kidnapped, though Janet seems to know exactly what has happened. Miss Petrie organizes a nationwide manhunt to find Amy, while Janet desperately tries to keep Amy apprised of the situation by calling, though Amy never hears any of Janet's phone messages. Amy tells Lucy of her dreams of running off to Barcelona, but Lucy and Amy are seen by a jealous Ninotchka, and she anonymously tips the D.E.B.S. to their location. The D.E.B.S. catch the two women having sex, causing Max storm out in disgust, followed by Dominique, Bobby and Janet. Though Lucy tries to reassure her, Amy returns, mortified, to the D.E.B.S. in attempts to explain herself.
Miss Petrie decides to exile her, but Max steps in with an alternative to save Amy's reputation and thus prevent the D.E.B.S. from looking foolish. Meanwhile, Lucy does everything she can to win Amy back, returning everything she has ever stolen, and with Scud's help, plans to crash the D.E.B.S. year-end dance, where Amy is to be made D.E.B. of the year. Lucy fights her way to the auditorium, and is just in time to hear Amy publicly give her speech about how awful it was to be Lucy's captive, but when Amy and Lucy meet eyes, Amy retracts her entire speech, and admits that the days she spent with Lucy were the best days of her life, before running offstage. She and Lucy find each other in a storage room very like the one in which they first met, and they share another long-awaited kiss. Max and the squad catch up to them, but Max reconciles herself with the fact that her best friend is in love. She lets them go and helps Amy and Lucy make their escape, later awarding Janet with her stripes. Lucy and Amy ride off into the night, heads on one another's shoulders.Sara Foster as Amy Bradshaw
Jordana Brewster as Lucy Diamond
Meagan Good as Max Brewer
Devon Aoki as Dominique
Jill Ritchie as Janet
Geoff Stults as Bobby Matthews
Jimmi Simpson as Scud
Holland Taylor as Mrs. Petrie
Michael Clarke Duncan as Mr. Phipps
Jessica Cauffiel as Ninotchka Kaprova
Aimee Garcia as Maria
Jennifer Carpenter as Hysterical student
Scoot McNairy as Stoner
Jill Ritchie was the only cast member from the short film to reprise her role in the expansion.
Director, writer, and editor Angela Robinson began to draw comics about the D.E.B.S. in college as a sideline to her writing (Robinson stated this in an extra on the U.S. DVD entitled "Infiltrating the D.E.B.S."). She received a $20,000 grant from Power Up to make a 11-minute short based on the concept, which toured a number of film festivals, including the Sundance Film Festival.
Michael Clarke Duncan and Geoff Stults would work again on The Finder, a spin-off of the series Bones. Their characters of Walter Sherman and Leo Know, played respectively, would be on the latter series. Fox canceled the series after the show's first season.
D.E.B.S. received a 40% "rotten" rating at Rotten Tomatoes based on 58 reviews.
D.E.B.S. was released in 45 theaters. Over 21 days, it grossed $97,446.