Misanagi is the Okashira (leader) of the Sanada Ninja clan, who guard the Divine Elixir. She decides to make a deal with the Black Knights, offering to help them locate and take the elixir, as long as they agree to give the Sanada control over Japan once their goals are achieved.
After they find the elixir the leader of the Black Knights (First Lieutenant Meldars), orders for Misanagi to be killed, saying that he was playing her all along and had no intention of giving Japan over to the Sanada, but controlling it along with the rest of the world. After suffering a deep shoulder cut due to a surprise attack by Second Lieutenant Lentz, she is unable to fight at her best and just as Lentz is about to finish her off, she is rescued by Second Lieutenant Schneider who, although loyal to the Black Knights, is disgusted by such a dishonourable act on his Meldars's part. Schneider is easily defeated by Meldars who is trained to fight on a horse, using a platinum lance. However, when Himura Kenshin arrives, Meldars is defeated by him after a hard-fought battle, but the heat and intensity of that battle causes the surrounding area to burn. Meldars, knowing that he has failed, does not attempt escape and allows himself to be consumed by the fire.
Initially wanting to remain in the flames and atone for having let the elixir be destroyed, Schneider influences Misanagi to live on, since he saved her life and nearly died as a result, and so she owes him that.
After the battle, Misanagi apologises to the Sanada clan and states that she is willing to accept any punishment they inflict on her, for having trusted the Black Knights, which led to the burning of the eilxir. Her clan, however, forgive her, understanding that she only wanted what was best for them and that she is best suited to be their leader.