The Alienist portrays LGBTQ+ characters primarily as victims of societal prejudice and violence in 19th-century New York. Their identities are sources of vulnerability, exploitation, and ultimately, tragic outcomes. While historically accurate, the net impact within the narrative is overwhelmingly negative, with little to no positive or affirming counterbalance.

Mary Palmer, a character described in the source novel with features implying a white European background, is portrayed by an actress of Indigenous heritage in the series.

The series portrays Christian institutions and certain adherents as hypocritical, cruel, or complicit in societal neglect. The serial killer's motivations are rooted in a twisted, fundamentalist interpretation of Christianity, which the narrative clearly depicts as pathological and destructive.

The film depicts Jewish characters and communities as victims of societal prejudice and anti-Semitism. The narrative frames this bigotry as wrong, positioning the audience to sympathize with the marginalized Jewish population.