BACKGROUND: Parkinson's disease (PD) leads to a significant decrease in brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). This study explores the effect of 12 weeks of multimodal exercise on the levels of BDNF and GDNF in patients with PD. METHODS: The study is a quasiexperimental study with random sampling. It was conducted in 2024 at Isfahan. Demographic data were collected using the demographic questionnaire outlined in the Methods section. Thirty patients were randomly divided into two equal groups of multimodal exercise and control, with no significant differences in age, weight, and height. The variables of BDNF and GDNF were assessed in pre- and post-tests. Multimodal exercise was performed 5 days a week for 12 weeks. Data were analyzed using covariance and -test at a significant level of < 0.05. RESULTS: The study observed significant differences in BDNF and GDNF, among two groups of PD ( < 0.01). Moreover, the levels of BDNF and GDNF were significantly higher in the PD + Training group compared to the PD group ( < 0. 01). CONCLUSIONS: Given that multimodal exercises are effective in increasing BDNF and GDNF in individuals with PD, it is recommended to incorporate the benefits of these exercises into physical rehabilitation programs. Therefore, the combined approach of multimodal exercises (resistance, aerobic, and balance) is recommended as the most effective complementary therapeutic strategy for PD.