Introduction: Studies suggest that exercise may be neuroprotective when implemented before the clinical presentation of Parkinson's disease (PD). Levels of brain-derived neurotrophic factor (BDNF), theorized to play a role in neuroprotection, are affected by its genotype and exercise. Here we explore this previously unstudied interaction on age at diagnosis and severity of symptoms. Methods: 76 participants with PD submitted buccal cells to determine BDNF genotype, completed the modified Lifetime Physical Activity Questionnaire to determine exercise habits, and were assessed using the Movement Disorder Society – Unified Parkinson's Disease Rating Scale III (MDS-UPDRS-III) and the Mini-Balance Evaluations Test (MBT). For aim 1 (age at diagnosis), 60 participants (age = 69.6 ± 7.4; males = 45, females = 15) were analyzed. For aim 2 (severity of symptoms), 54 participants (age = 70.0 ± 7.6; males = 41, females = 13) were analyzed. Results: The final hierarchical regression model for age at diagnosis produced an R2 = 0.146, p = .033; however, the only significant variable in the final model was average moderate physical activity from ages 20s to 40s (p = .009). The regression for MDS-UPDRS III was not significant; however, the regression for MBT was, p = .0499. In the final model, 23.1% of the variance was explained. Years since diagnosis (p = .014) and average vigorous physical activity from ages 20s to 40s (p = .047) were the only predictors in the final model. Conclusions: While a strong interaction between BDNF genotype and lifetime physical activity was not observed, our results suggest that lifetime exercise may be neuroprotective in PD. Specifically, higher amounts of moderate PA were associated with an older age at diagnosis.