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Parkinson's disease (PD) is a neurodegenerative disease characterized by dyskinesia and related to microglia-mediated pyroptosis. Stem cell-derived exosomes have small size, low immunogenicity, and the ability of transferring the effective substances of stem cells freely. In this study, exosomes were isolated from human umbilical cord mesenchymal stem cells (hucMSCs) and injected into PD rats induced by 6-hydroxydopamine (6-OHDA). We found that the exosomes were absorbed by dopaminergic neurons and microglia in the affected side and exosome treatment inhibited microglia activation and prevented nigral-striatal dopamine neuron damage. Furthermore, pretreatment cultured BV2 cells with exosomes inhibited TLR4/NF-κB/NLRP3 inflammasome induced by LPS/ATP. Therefore, exosomes inhibited pyroptosis and reduced the secretion of supernatant IL-1β and IL-18, improved the survival rate of SH-SY5Y. In addition, the potential targets of hucMSCs- exosomes treatment of PD was further identified by miRNA high throughput sequencing and protein spectrum sequencing.