The show offers a consistently positive and affirming portrayal of LGBTQ+ characters and themes. It depicts diverse queer identities and relationships with depth, agency, and normalcy, particularly through Leighton's coming-out journey and other characters' sexual explorations. Challenges are framed as external or internal struggles, reinforcing the worth of queer lives within a supportive narrative.

The Sex Lives of College Girls features Willow, a trans woman, as a significant, well-rounded character and love interest. The show respectfully portrays her identity, focusing on her confidence and agency. Through Leighton's journey of acceptance, the narrative normalizes and affirms a trans romantic relationship, presenting Willow's identity as a natural and valued aspect of her character.

The show satirizes the hypocrisy of public figures, specifically Senator Chase, who leverage a conservative Christian image for political gain while their private actions contradict these values. The narrative critiques the performative and opportunistic use of faith by some adherents.