A two-player game for the Wii. This game features both Luigi and Waluigi as the stars and Princess Daisy as the damsel in distress. Rui, who is acting as the main antagonist, is "rejected" by Daisy, which finally drove him insane, which led to Rui dragging Daisy by her hair to his castle. Waluigi attempts to stop Rui, but underestimated him because of the boy's size and, as a result, Waluigi was knocked off a cliff into the western ocean. After a week of swimming, Waluigi washes up on the Mushroom shore. Luigi, who happen to be on a vacation, asked Waluigi what happened and aftwards the two make their way to the Western Territories and, after traversing many terrains and overcoming many obstacles, Luigi and Waluigi finally come to Daxian's castle, where Rui is "hanging" with Daisy. After a long, arduos battle the two defeat Rui, and he surrenders Daisy and runs away crying.
- Princess Daisy- Daisy is only playable as she tries to get away from Rui. Daisy ultimately fails and is dragged by her hair to Daxian's castle. Daisy is not playable for the remainder of the game.
- Luigi- Luigi is playable after the "Waluigi" stage.
- Waluigi- Waluigi is playable after the "Waluigi" stage.
- Rui- Rui is only playable during the "Waluigi" stage. Rui is not playable for the remainder of the game.
Protagonistic Non-Playable Characters
- Shy Guy Bros.- Four Shy Guys that help Luigi and Waluigi by training them and teaching them new abilities.
- Mario- Gives Luigi and Waluigi useful items via information letters.
- Wario- Gives Luigi and Waluigi useful items via telegram.
- Toadette- appears as the damsel in distress in the "Boo Island" stage. Upon being rescued, she rewards you with the Dragon Coin, which enables Dragon-Man transformation.
Antagonistic Non-Playable characters
- Tatanga- Tatanga finally makes a reapearance as the Boss of the "Sky Tower" stage.
- Popple- Popple, having his memory restored, travels to the west and confronts Luigi and Waluigi in the "Boo Island" stage, and again in the "White Pyramid" stage.
- Koopa Bros.- When Luigi and Waluigi traverse Koopa Bay, the Koopa Bros., finding themselves in the West after a storm, challenge the pair to an all-out battle, mistaking Luigi for Mario.
- King Boo- King Boo is the Boss of the "Boo Island" stage and "Spirit Cave" stage.
- King Gool- The Boss of Dark Pyramid.
- Petey Piranha- The Boss of Piranha Plains.
- Magmius- The boss of Mt. Magma.
- Sarasaland- First stage in which Daisy attemps to escape from Rui.
- Waluigi- Rui battles Waluigi in this stage.
- Sky Tower- This aerial stage requires teamwork between Luigi and Waluigi.
- Tatanga- Tatanga is fought in this stage before using the Trans-Star
- Koopa Bay- After being transported, Luigi and Waluigi will land in Koopa Bay, which they must get through.
- Koopa Bros.- The Koopa Bros. mistake Luigi for Mario and challenge Luigi and Waluigi to a fight.
- Boo Island- After accidentally being warped into Boo Island, Waluigi defeats the Koopa Bros. and Luigi hears faint shreiking. Luigi convinces Waluigi to help him find the source of the shreiking. Along the way Popple appears and tries to stop them, but Waluigi stomps him into the ground.
- King Boo- After finding Toadette, the shreiker, and King Boo must be defeated.
- Spirit Cave- Luigi and Waluigi discover a cave which leads to the mainland and decide to explore the cave.
- King Boom Boo- King Boo must be defeated once again. However the battle is made more dificult because King Boo absorbs four Gold Boos, becoming King Boom Boo.
- Piranha Plains- After defeating King Boom Boo, Luigi and Waluigi are transported to Piranha Plains and begin to trek along the plains.
- Petey Piranha- Petey Piranha must be defeated.
- Mt. Magma- A volcano which Luigi and Waluigi must cross.
- Magmius- A magma monster that must be defeated.
- White Pyramid- A beatiful white pyramid that Waluigi finds and, motivated by the of treasure, rushes in with Luigi dragging by his long arm.
- Popple- Popple infuses with the White Golem and must be defeated.
- Dark Pyramid- A spooky pyramid Luigi and Waluigi find themselves lost in.
- King Gool- King Gool, which Luigi inadvertedly summoned, appears and must be defeated.
- Daxian's Castle- Luigi and Waluigi finally make it to Daxian's Castle where Rui and Daisy are.
- Rui- In the final battle, Rui must be defeated.