People with HIV (PWH) experience a high frequency of symptoms that are associated with poor clinical outcomes. We conducted a secondary analysis of data from an observational study to examine whether diet, muscle strength, or physical activity were associated with symptoms among PWH and their HIV-uninfected peers. One-hundred ninety-one individuals (105 PWH and 86 HIV uninfected) with similar age and race were included. Symptoms were examined using the Patient-Reported Outcomes Measurement Information System (PROMIS-29) questionnaire, for which lower scores indicate higher function or fewer symptoms. The total healthy eating index score and carbohydrates, sugar sweet beverages, alcohol, and fiber consumption per day were obtained through 24-hour dietary recalls. A dynamometer was used to determine muscle strength. Steps per day were examined through 7 days of actigraphy. Linear regression analyses were used to determine the relationship between symptoms and diet, muscle strength, and steps per day. Participants were, on average, 54 years, 83% were African American, and 58% were male. In PWH, less healthy eating, fiber intake, and muscle strength were associated with poorer physical function; more steps per day were associated with fatigue; less daily carbohydrate consumption was associated with more pain. HIV-uninfected individuals demonstrated an association between fewer steps per day and poorer physical function and more pain, and less carbohydrate intake and more sleep disturbance. The relationships between diet, muscle strength, steps per day and PROMIS-29 health domains differed by HIV status.