The Girls' Room is a skit that takes place in the girls' bathroom of a high school, but for one episode, took place in the boys' bathroom of the same school. The characters are Amber (played by Amanda Bynes), an egotistical and school mean girl who always makes sure to remind the audience that she is popular (although this just may be in her own mind, as in one skit, a girl was asked what made Amber so popular, the girl responded that she didn't know who Amber was; in another skit, Amber was neither asked to the prom nor voted prom queen), Sheila (played by Raquel Lee in season 1 and Reagan Gomez-Preston in seasons 2-3), an aggressive black girl who disposes of unwelcomed guests by giving them swirlies (usually executing them in the middle stall), Tammy (played by Jamie Snow), an "exchange student" from Tennessee, and Debbie (played by Jenna Morrison), an unintelligent girl who constantly says that she likes eggs, and constantly bothers the others, especially Sheila. Amber has a rivalry with another, much more popular girl, Danielle Spencer, (played by Serah D'Laine) who always seems to one up Amber, but usually ends up getting a swirly from Sheila. Drake Bell occasionally appears as Jeremy Pivers, the most popular boy in school and is a one-sided Amber's love interest.
- The Girls' Room: The Girls' Room take place in a girls' bathroom and stars teenagers Amber (Amanda Bynes) the most popular girl in school, a bad girl named Sheila (Raquel Lee), an exchange student from Tennessee named Tammy (Jamie Snow), and a stupid girl named Debbie (Jenna Morrison) as they talk about a pop quiz they just had conducted by Miss Yumbo. Then they talk about Josh Elliott who doesn't like either of them causing Sheila to give him a swirly.
- Voting: Sheila, Tammy and Debbie are voting for Amber for class president. When Caroline has not decided who she is voting for, Sheila gives her a swirly and finally gets her to vote for Amber. Amber's rival Danielle Spencer is also running for president and mentions that a third candidate named Jamie Bradford has joined the election. When Amber had Shelia bring Jamie to the Girls' Room, the girls are surprised that Jamie is really a boy. Danielle Spencer and Amber lastly drop out of the race and give the support to Jamie Bradford.
- Girls' Choice Awards: Amber, Sheila, Tammy and Debbie host the annual "Girls' Choice Awards." (parody of Nickelodeon's KCAs) The first award deals with the "Worst Cafeteria Food Served" with Pork Loaf winning over Sloppy Joes, Noodle Goo, and Fishburgers with the cafeteria lady Miss Shapein accepting the award on the behalf of Pork Loaf, after Debbie says "Faol Krop" and is later corrected by Sheila and finally says "Pork Loaf". The second award deals with the "Best Cable TV Show" with "The Girls' Room" winning over "Good Morning Chess Club," "Cooking with Miss Shapein," and "Locker Room Hygiene with Coach Squaddle" much to the objection of Coach Squaddle. The final award deals with the "Most Popular Girl in School" where Tina Capone wins over Amber (who was nominated three times). When Sheila gives Tina Capone a swirly while Tina cannot accept the final award, Amber is happy to accept the final award on her behalf.
- Auditions: Amber, Sheila, Tammy and Debbie hold auditions to add a new girl to their group. The first girl is Lauren Thomas who is asked by Sheila why Amber is popular. Lauren doesn't know who Amber is and is rejected. Sheila gives Lauren a swirly. The second girl is Terry Garner who is asked by Tammy what is her favorite thing to do. Terry is too talkative and is rejected, and Sheila gives Terry a swirly. The third girl is Penny Nickel who is asked by Debbie what one item she would bring if she was stranded on a deserted island. Penny couldn't make up her mind on what item to bring and is frightened into the bathroom stall by Sheila.
- Talent Show: Amber, Sheila, Tammy and Debbie hold a talent contest. The first act deals with Dustin Puddin trying to do a magic trick involving making a cake appear out of a hat, but it doesn't go well, and Sheila gives him a swirly first. Then Miss Shapein does an interpretive dance with a melon, which annoys Sheila who gives her a swirly. Kyle Rostensan tells a story. Just as Sheila attempts to give Kyle a swirly, Debbie interrupts her and asks she give him a swirly. As an excuse to make out with Kyle in a bathroom stall, Debbie explains that she has never given a kid a swirly before.
- The Boys' Room: The show is coming from the Boys' Room when there is a water pipe burst in the Girls' Room. After having exited the Girls' Room that is flooded, Debbie arrives in the Boys' Room and mistakes a urinal for a waterfall machine. Amber has Sheila make two boys named Tad and Chuck model two gowns that were worn to last week's dance: one that was worn by Amber and another one that was worn by Tina Capone. Sheila gives Tad and Chuck both swirlies, and the two boys are dressed in gowns by Sheila. When the coach tries to restore order in the Boys' Room, he ends up getting a swirly from Sheila which he enjoys.
- Prom Night: It's prom night at Kawaga Junior High, and Debbie arrives late with a dark orange sunburn after falling asleep in the tanning salon. Amber tries to convince Principal Hazzmat to make her Prom Queen. Hazzmat tries to get the girls and the cameramen to leave the bathroom, and under orders from Amber, Sheila gives him a swirly. Hazzmat leaves. Amber then hears from some girls that Jeremy Pembers has been elected as Prom King and sends Sheila to get him and congratulate him personally. Amber then hears from some girls that Danielle Spencer has been elected Prom Queen and has Sheila bring Danielle to her. Amber then usurps Danielle's position and then forces Jeremy to dance with her while Sheila gives Danielle a swirly.
- Amber's Birthday: Debbie calls herself "Elizabeth", and Amber corrects her and calls her "Debbie". Sheila, Tammy, and Debbie celebrate Amber's birthday and each give her a present. Sheila reminds Amber to open the present before Debbie, whom Sheila calls "Elizabeth", pushes her over the edge. Debbie gives Amber eggs while Tammy brings in a cake containing a dancing kid in a firefighter outfit. Amber, Sheila, Tammy, and Debbie stop him from dancing the Vegas strip, and Sheila gives him a swirly. Danielle Spencer arrives and Debbie likes her new dress. When it comes to Sheila's present, she discards it in order to steal Danielle's new dress and to hand it to Amber, leaving Danielle in her underwear.