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The aim of the study was to investigate the association of physical activity in three categories (inactive, insufficiently active and active) with health outcomes in people with epilepsy. The dependent variables and the instruments used in the study were: a) quality of life — measured by Quality of Life in Epilepsy-31 for adults and Quality of Life in Epilepsy for Adolescents, b) side effects of medication — measured by Adverse Events Profile, c) depression — measured by Neurological Disorders Depression Inventory for Epilepsy, and d) state and trait anxiety — measured by State–Trait Anxiety Inventory. Physical activity levels were analyzed using the International Physical Activity Questionnaire (IPAQ) for adults in the commuting and leisure domains and Physical Activity Questionnaire for Adolescents (PAQ-A). Simple and multiple linear regression was used in the statistical analysis. The cross-sectional study with one hundred and one individuals was conducted in Pelotas/RS, Brazil, at the Neurology Clinic of the Faculty of Medicine of the Federal University of Pelotas. In the crude analysis, physical activity was positively associated with quality of life (p < 0.001) and negatively associated with depression (p = 0.046), state of anxiety (p = 0.014), trait of anxiety (p = 0.015) and side effect of medication (p = 0.01). In addition, physical activity levels explained 10% of the quality of life (R2 = 0.10). In the adjusted analysis, physical activity remained associated with side effect of medication (p = 0.014) and was not associated with trait anxiety (p = 0.066). However, quality of life showed a positive linear trend (p = 0.001) while depression (p = 0.033) and anxiety state (p = 0.004) showed a negative trend according to physical activity levels. Physical activity was associated with health outcomes, and can be a nonpharmacological treatment in people with epilepsy for improving health and life conditions.