Monkey D. Luffy serves as the central protagonist in this retelling of the Drum Island storyline. When Nami collapses with a severe fever during a storm, Luffy spearheads the crew's urgent mission for medical aid. Upon reaching Drum Island, he personally apologizes to hostile residents and begs for assistance to save Nami, demonstrating his willingness to humble himself for his crew. He then carries Nami up the treacherous frozen mountain to Dr. Kureha's castle, enduring extreme cold and physical hardship. An avalanche buries Sanji during the climb, but Luffy perseveres with Nami, nearly succumbing to the elements before summiting.

At the castle, Luffy interacts with Tony Tony Chopper and witnesses his medical skills treating Nami. Later, when Wapol and his brother Musshuru attack to reclaim Drum Island, Luffy confronts Musshuru directly. Initially overpowered by Musshuru's speed and poisoned by toxic spores, Luffy requires Robin's antidote. After recovering, he activates Gear Second to match Musshuru's velocity and defeats him. When Wapol fuses with Musshuru and the Bliking Cannon into a composite form, Luffy employs Gear Third's Gigant Pistol to deliver the final blow, launching Wapol from the island. He physically protects Dr. Hiriluk's flag from Wapol's destruction, symbolizing respect for Chopper's past and ideals.

Following the battle, Luffy invites Chopper to join the Straw Hat Pirates as their doctor. Chopper hesitates due to past acceptance struggles, but Luffy's persistent invitation and the crew's camaraderie persuade him. This recruitment occurs despite Kureha's objections, and Luffy departs Drum Island with his new crewmember. The film incorporates elements from later in the overarching storyline, including Luffy's Gear Second and Gear Third abilities, indicating a post-Enies Lobby Arc timeline. Crew members absent in the original Drum Island arc, such as Nico Robin and Franky, participate, and the Thousand Sunny replaces the Going Merry as their ship.