Mario is one of the three main characters in the game(while Luigi and Bowser being the other two). Mario possesses the same abilities as Luigi and is inhaled into Bowser's Body as well. The Bros. and Starlow help Bowser get his castle back from Fawful. Along the way, Bowser meets Broque Monsieur and Broggy and gets the ability of the Vacuum Block. Mario, Luigi, and Starlow aids Bowser in his trips, while they travel to various parts of his body. When Bowser finally reaches his castle and reclaims it, Bowser is grown fat from winning the fight against Midbus, a giant pig.
While Bowser is fat, Mario and Luigi find Peach in the Flab Zone, who is kidnapped in front of them by Kretins. After a long chase, Mario and Luigi trap and defeat Alpha and Beta Kretin, freeing the Princess. Peach, after the boss battle, tells them that Fawful probably wants the Dark Star, so he can control the Mushroom Kingdom. She also explains that Peach herself is necessary for this process. As they find an exit, Peach is taken out of Bowser's Body by Fawful and is once again kidnapped. Meanwhile, Midbus gives Bowser a treadmill to lose his extra pounds on.
Mario and Luigi travel until they find Bowser knocked out in a island of trash. After fighting Junker, they go back into Bowser, and wake him up from his back pain. After going through the castle all to finding the Dark Star awakening and Fawful becoming Dark Fawful, who is sent flying by Bowser. Dark Star enters Bowser, who copies his DNA, but is incomplete thanks to the Mario Bros., and combines with Dark Fawful to create Dark Bowser.
After Mario and Luigi defeat Dark Star Core and Bowser defeats Dark Bowser, Fawful explodes, destroying himself, and expelling everyone else from Bowser's body, freeing them. After realizing that the Mario's were inside Bowser, Bowser and Mario & Luigi fight, which ends the story. At the end, it is revealed that Mario and Luigi win yet again and Bowser is back at his ruined castle, recovering from the injuries he sustained in their fight.