The Sopranos features Vito Spatafore, a high-ranking mobster whose secret homosexuality is revealed. His identity becomes a source of intense conflict and ultimately leads to his brutal murder by his peers. The narrative depicts the severe, violent homophobia prevalent in the mob world, resulting in a net negative portrayal for LGBTQ+ themes.

The Sopranos includes a minor storyline involving Carmine Lupertazzi Sr.'s grandchild, Carmela, who is a trans woman. The narrative primarily focuses on Carmine Sr.'s struggle for acceptance within his traditional family context. The portrayal avoids strong positive affirmation or negative ridicule, instead presenting the identity as a challenge to established norms, resulting in a neutral overall impact.

The series consistently portrays its Catholic adherents, particularly the main characters, as deeply hypocritical. They selectively engage with religious practices and beliefs, using them to assuage guilt or justify actions, while fundamentally failing to adhere to core moral tenets. The narrative highlights this disconnect without offering a significant counterbalancing positive portrayal of the faith's practice among its central figures.

The series portrays Jewish characters with complexity and dignity, such as Dr. Melfi and Hesh Rabkin. While characters like Tony Soprano express anti-Semitic views, the narrative clearly frames these as the bigotry of a flawed individual, positioning the audience to condemn such prejudice rather than the religion itself.