Nezuko's original personality as a human was that of a kind and caring girl, who thought of others before herself much like her older brother Tanjiro. She was a responsible elder sister to her younger siblings.

As a demon, Nezuko seems to have forgotten a good portion of her memories as a human, besides those related to her family. She is still very caring and protective towards other humans who she sees as members of her family due to Urokodaki's influence while she was asleep for two years. She is also rather brazen, and does not seem to fear fighting; she fiercely guards her brother as well as her allies. She also developed a strong willpower as she refused to consume human flesh or blood, even in cases of extreme injury or exposure to human blood, such as Sanemi Shinazugawa's Marechi blood.

She still retains her human emotions, as she has been seen to cry and be happy, but in general she appears more detached than her human cohorts, as well as calmer and less malicious than most demons.

As a demon, Nezuko does not talk often and stutters a lot. This may be due to her bamboo mouthpiece, which is seldom removed. It also means she is sometimes hard to read.