Harlem offers a predominantly positive portrayal of LGBTQ+ characters, primarily through Quinn, a main character. Her journey as a lesbian woman is depicted with depth, humor, and dignity, normalizing queer relationships and experiences. The show affirms LGBTQ+ lives by presenting complex characters and storylines without resorting to harmful stereotypes or making identity a source of degradation.

The show features Ian, a trans man, as a significant love interest for one of the main characters. His identity is explored with dignity and complexity, focusing on themes of acceptance and love. While initial challenges arise from a cis character's perspective, the narrative ultimately affirms trans identity and relationships, portraying Ian as a well-rounded and desirable individual.

The series portrays Christianity, particularly through Quinn's mother, Patricia, as a sincere and foundational aspect of her life and community. While comedic situations arise from generational differences, the narrative consistently depicts the church as a supportive institution and faith as a source of strength and purpose, without undermining its virtues.