Our Idiot Brother features a character, Dylan, who is revealed to be gay. The film depicts the consequences of his infidelity and secrecy within his marriage, rather than focusing on or condemning his sexual orientation. His gay identity is presented factually, without strong positive affirmation or negative degradation, contributing to a neutral overall portrayal.

The film includes a trans man, Janet, as the new partner of a character's ex. Janet's trans identity is present as a plot point but is not central to the narrative. The portrayal is incidental, neither uplifting nor denigrating, as Janet is not a developed character and their identity serves primarily as a catalyst for another character's emotional arc.