Ratched features prominent LGBTQ+ characters, most notably Mildred Ratched and Gwendolyn Briggs, whose central romantic relationship is depicted with depth and dignity. While acknowledging the historical prejudice and dangers faced by queer individuals in the era, the show frames these as external obstacles. The narrative affirms the worth of their love and identity, making the overall portrayal primarily positive.

The show features Henry Osgood, a character who expresses a desire to be a woman. His transsexual identity is depicted as the reason for his institutionalization and subsequent lobotomy. While the series critiques the unethical medical practices of the era, Henry's journey is one of unrelieved misery and degradation, offering no positive or affirming portrayal of transsexual identity.

The series portrays Christian institutions, particularly an orphanage, as sources of profound trauma and abuse for key characters. Religious figures are often depicted as complicit in societal injustices or ineffective in providing genuine moral guidance, highlighting hypocrisy and the failure of traditional morality within the narrative.