NYPD Blue featured Detective John Irvin, a recurring gay character whose arc explored his coming out and professional life with dignity. While facing initial prejudice, the show ultimately depicted his identity and relationships with empathy and complexity, framing obstacles as external and affirming the worth of LGBTQ+ lives within a realistic police drama context.

NYPD Blue featured transsexual characters, notably in an episode depicting a trans woman as a victim of a hate crime. While the narrative condemned the violence and sought justice, reflecting an empathetic stance, the portrayal also included problematic elements common for its era, such as the character's tragic circumstances, sex worker stereotype, and misgendering by some characters. The net impact is neutral, as the show's positive message against prejudice is balanced by these problematic depictions.

The show explores the complexities of Christian faith, depicting both the moral failings of some adherents and institutions, and the genuine comfort and ethical guidance it provides to others. Critiques are often framed as human hypocrisy rather than inherent flaws in the faith itself.

While less central, Islam is generally portrayed as a respected part of the city's diverse population. Muslim characters are depicted as individuals, and the narrative avoids negative generalizations or critiques of the faith itself.

Judaism is depicted respectfully as part of New York City's diverse cultural and religious landscape. Jewish characters are portrayed as individuals, and their faith or background is integrated without negative stereotyping or judgment of the religion itself.