When the Mario Bros. reach the ruined Castle Town, they immediately go to the castle, where they meet Lady Lima. She tells them to fix the castle's plumbing. When they do, the Beanstar's protective barrier vanishes and "Lady Lima" reveals herself to be Cackletta. When the Mario Bros. reach the room, she forces Queen Bean to attack them and leaves before the fight.
Her next appearance is in Woohoo Hooniversity, where she apparently turned all the scientists into monsters. After Peach's voice fails to awaken the Beanstar (because, as it turns out, the voice that Cackletta had stolen at the start of the game was actually that of Birdo's), the Mario Bros. come in and defeat her. Fawful sucks her spirit up with his headgear and prepares to blast Mario and Luigi. Prince Peasley then knocks Fawful and Cackletta's spirit to Stardust Fields.
There, a battered and beaten Fawful finds Bowser's unconscious body, and allows Cackletta to possess him. She then becomes Bowletta, a rather frightening hybrid of Bowser and Cackletta herself. She then takes control of both Beanbean and Koopa troops in a final battle against the Mario Brothers. The Mario Brothers then fight the Koopalings and Fawful throughout Bowser's Castle. Then they go for Bowletta, herself. After an initial battle with Bowletta, the Mario Brothers are taken inside of Bowletta as she cheats and nearly kills them. Cackletta's spirit then is confronted by Mario and Luigi for a final fight. After the spirit's defeat, Cackletta is defeated once and for all.
- During the first fight with Cackletta, there is an easy way to tell which is the real Cackletta when she uses the Clone attack. The real Cackletta always uses both arms for the lightning attack. The ones that just use the left or right arms are the fakes.
- Cackletta is very similar to Elder Princess Shroob: They both take over Bowser at the end of the game (though Bowser keeps his sanity while Elder Princess Shroob is controlling him).
- Cackletta is the only main antagonist that is fought right at the middle of the game rather than the end.
- However, technically, she is fought a total of three times throughout the game: At Woohoo Hooniversity, as Bowletta at the end, and finally as a soul at the very end of the game. This makes her the most fought main antagonist out of all Mario RPG games.
- Though, Bowser from Paper Mario also holds the record for the most fought times being three as well: At the beginning of the game (which cannot be won at any means), inside Princess Peach's Castle, and finally on a platform in the sky.
- Cackletta is the first female antagonist in a Mario RPG game. The second is the Shadow Queen from Paper Mario: The Thousand-Year Door, and the third is Princess Shroob/Elder Princess Shroob from Mario & Luigi: Partners in Time.