Introduction: Depression is a common mood disorder in patients with Parkinson’s disease (PD), which negatively influences the quality of life and enhances caregiver burden. MLC901, a traditional medicine, has been demonstrated to be useful in preclinical and clinical studies. The aim was to study the effect of MLC901 on depression behavior in a mouse model of PD, comprising in the unilateral striatal delivery of the neurotoxin 6-hydroxydopamine (6-OHDA). Methods: Female NMRI mice were divided into the following groups: sham/saline group, 6-OHDA/saline group, sham/MLC901 (40μg/kg) group and 6-OHDA/MLC901 group. Intraperitoneal treatments of MLC901 were started one week after the stereotaxic surgery that continued for 4 weeks (5 days/week). Locomotion was monitored using an openfield test and depressive-like responses were measured by forced swim test (FST) and tail suspension test (TST). Results: We found that MLC901 prevented the increased immobility time in the PD mice in both FST and TST, suggesting an antidepressant efficacy for the MLC901. None of the treatments alter locomotion compared to the sham group. Conclusion: In conclusion, we propose that MLC901 is a potential candidate to be used in studies for the treatment of depression in PD.