Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. Dopamine (DA) replacement therapy is one of the most effective drug treatments for PD; however, long-term levodopa treatment can lead to various side effects that negatively impact the quality of life of patients. Therefore, finding safe and effective alternative drugs to treat PD is of clinical importance. The Bushen-Jianpi decoction (BSJPD) was derived from classic traditional Chinese medicine and has been shown to be effective in the treatment of PD. This study explored the effects and mechanisms of action of BSJPD in PD. In our study, rats were randomly divided into six groups: the vehicle group, rotenone (ROT) + Saline group, ROT + low-dose BSJPD group, ROT + high-dose BSJPD group, ROT + Madopar group, and ROT + low-dose BSJPD + Madopar group. Treatment was administered to the rats once a day for 28 days, and behavioral tests were assessed. Tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT), monoamine oxidase B (MAO-B), dopa decarboxylase (DDC), alpha-synuclein (α-syn), and heme oxygenase-1 (HO-1) levels were detected. Our results show that BSJPD increases the body weight of rats, improves their motor coordination, reverses decreasing TH levels in the SN, and increases the expression level of DDC and HO-1 in the striatum (ST), but it fails to affect TH levels in the ST in the PD model. In addition, BSJPD reduced the expression of MAO-B in the ST in the PD model, but it did not have a significant effect on COMT. Rather, COMT in the plasma and liver increased in the low-dose BSJPD treatment group. Upregulation of α-syn in the PD model was also observed, but BSJPD has shown no obvious effect to clear it. Our results suggest that BSJPD exhibits a therapeutic effect on PD and may play a neuroprotective role by regulating HO-1 expression and participating in the metabolic process of DA.Copyright © 2022 Wei Liang et al.