The show features Jenny, an openly lesbian main character, whose sexuality is a consistent part of her portrayal. While her identity is often used for comedic purposes, sometimes relying on stereotypes, she is also integrated into the family and her relationships are depicted. The portrayal avoids strong affirmation or degradation, resulting in a largely neutral impact.

Two and a Half Men features the character of Miss Pasternak/Marty, whose gender identity and transitions are primarily used for comedic shock value and awkward humor. The portrayal lacks dignity and complexity, with the character's journey of transitioning to female and then back to male serving as a plot device for laughs rather than an empathetic exploration of identity. The net impact is negative.

The show frequently uses Christian-coded morality as a target for satire, often depicting characters who adhere to or preach such values as hypocritical, judgmental, or out of touch. The narrative generally undermines traditional religious virtues in favor of hedonism or secular pragmatism.