Makoto Shishio is the primary antagonist of the Rurouni Kenshin: New Kyoto Arc, a former hitokiri (manslayer) who once served as the successor to Himura Kenshin during the Bakumatsu period. His background is defined by betrayal: after the Meiji Restoration, the new government deemed him a threat due to his knowledge of its secrets and his ambitious nature, and they attempted to eliminate him by knocking him unconscious, dousing him in oil, and burning him alive. Shishio survived, but the ordeal left his entire body severely disfigured, forcing him to wear bandages constantly to cover his scarred skin. The burns also destroyed his sweat glands, meaning his body cannot regulate temperature naturally; any fight lasting more than about fifteen minutes risks fatal overheating or spontaneous combustion. This physical limitation is a crucial weakness that shapes his combat strategy.

Personality-wise, Shishio is ruthless, coldhearted, and highly intelligent. He operates with an unwavering belief in social Darwinism, often stating that the strong eat the weak, and he views compassion and mercy as signs of weakness. Despite his cruelty, he possesses a dark charisma that inspires fanatical loyalty in his followers, and he is capable of strategic brilliance, having hidden from the Meiji government for years while assembling his forces. His motivation is twofold: a deep-seated desire for revenge against the government that betrayed him, and an ambition to conquer Japan and reshape it according to his philosophy of natural selection, including plans to strengthen the economy through petroleum.

In the story, Shishio serves as the central obstacle during the Kyoto Arc. He leads a powerful group of elite warriors known as the Juppongatana (Ten Swords), and his goal is to overthrow the Meiji government and install himself as ruler. His role forces Kenshin to confront his own past as a killer and to test his vow never to take another life. The conflict builds to a climactic battle between Shishio and Kenshin aboard a ship, where Shishio's physical limits ultimately cause his downfall—his body overheats and bursts into flames during the fight, leading to his death.

Key relationships define Shishio's character. His lover, Komagata Yumi, is a former high-ranking geisha who stands by him unconditionally, and he shows genuine affection for her, even as he ultimately uses her as a shield at a critical moment. Seta Sojiro, the strongest of the Juppongatana, is Shishio's ideological disciple and right-hand man; Shishio molded Sojiro to embody his philosophy of the strong dominating the weak. His relationship with Kenshin is one of supreme rivalry—Shishio sees Kenshin as the only person capable of challenging him, and their clash represents an ideological battle between mercy and might.

Notable abilities include extraordinary swordsmanship on par with Kenshin in his prime. Shishio wields a custom katana called the Infinite Blade, which has a serrated edge and is coated with oil from past victims. By using friction, he can ignite the oil and perform fire-based techniques such as Homura Dama (Flame Bullet) and Guren Kaina (Crimson Lotus Arm), which add destructive, burning properties to his attacks. He is also a tactical genius, capable of manipulating events and people to his advantage, and his endurance is remarkable given his injuries. While he does not undergo significant character development—remaining unrepentant and resolute to the end—his role in the narrative underscores the themes of redemption, the cost of violence, and the question of whether absolute power can be used for good.