The Middleman features Noser, a prominent gay supporting character whose identity is depicted with consistent dignity and normalcy. His relationship is presented without fanfare or conflict, seamlessly integrated into the show's quirky world. The portrayal avoids stereotypes, contributing to an overall affirming and respectful representation of an LGBTQ+ character.

The show features female characters who engage in and win physical combat against male opponents. Ida, an android, frequently uses her enhanced strength and combat skills to subdue male adversaries in close quarters. Wendy Watson also defeats a male vampire in a melee weapon fight.

The character Noser, who was depicted as white in the original comic book series, is portrayed by a Black actor in the television adaptation, constituting a race swap.