Due to sealing away her emotions, Mukuro treats Shido with general indifference, not even reacting when Shido was forced to act on the Fraxinus crew's perverted command. Nevertheless, Mukuro still listen to Shido's explanation and reasons for wanting to seal her power. However, Mukuro plainly calls him out for his hypocrisy, questioning if she wouldn't be placed in more danger by DEM if her powers were sealed. In the end, Mukuro's words cause Shido to suffer a minor depression, which wasn't cured until he met with his counterpart in the fantasy world.
After having her heart unlocked, Mukuro becomes deeply attached to Shido after seeing his efforts in saving her, and that they were both once lonely orphans that felt empty and were starving for love. Due to becoming attached to Shido, she refused to share him with the others, even locking the memories of all of Shido's friends and family in the process. However, after Shido was able to figure out her past, he was able to calm her down from inversing after seeing him injured. Afterwards, Mukuro refers to Shido as her family, and permits that he be the only one she is willing to let cut her hair.