This study investigates the effects of hydrogen sulfide (H2S) molecules on the Nrf2 (nuclear factor E2-related factor 2)/HO-1 (heme oxygenase-1) pathway in a mouse model of Parkinson's disease (PD), aiming to elucidate the neuroprotective mechanism of hydrogen sulfide therapy for PD. Real-time fluorescence quantitative PCR was employed to measure the expression levels of glutathione peroxidase (GSH-Px) mRNA, superoxide dismutase (SOD), and Nrf2 in the striatum of the mice. Additionally, Western blot analysis was conducted to assess the protein expression levels of TH and the Nrf2/HO-1 pathway in the striatal tissue. The results indicated that the expression levels of CAT, GSH-Px mRNA, SOD, and Nrf2 showed significant differences between the experimental group and the control group, with notable increases in TH and Nrf2/HO-1 expression (P<0.05). In conclusion, hydrogen sulfide can upregulate the expression levels of Nrf2/HO-1 in the cerebral striatum of PD mice, contributing to its therapeutic effects.