Hot in Cleveland features a recurring gay character, Tony Chase, who is consistently portrayed with dignity and agency. His identity is affirmed, and his relationships are treated with normalcy, contributing to a net positive and validating depiction of LGBTQ+ individuals within the sitcom format.

The show features a transsexual character, Frederica, whose identity is revealed as a comedic plot twist in one episode. The portrayal is neutral, as the humor is derived from the situational surprise rather than mocking Frederica's identity. The character is not depicted with significant depth or agency, nor is her identity presented as inherently problematic or a source of degradation.