Objective To investigate the correlation of serum nerve-derived exosomes miR-221 and miR-214 with cognitive impairment in Parkinson’s disease （PD）.Methods A total of 150 patients with PD were enrolled as PD group and 100 healthy individuals who underwent physical examination were enrolled as control group. According to the degree of cognitive impairment， the PD group was divided into normal group （PD-N group）， mild cognitive impairment group （PD-MCI group）， and dementia group （PD-D group）. Quantitative real-time PCR was used to measure the expression levels of the exosomes miR-221 and miR-214； a Pearson correlation analysis was used to investigate the correlation of the expression of miR-221 and miR-214 with the scores of Unified Parkinson’s Disease Rating Scale （UPDRS） and Montreal Cognitive Assessment （MoCA）； the receiver operating characteristic （ROC） curve was plotted to analyze the value of the expression of miR-221 and miR-214 in predicting cognitive impairment in PD.Results The PD group had significantly lower expression levels of the serum nerve-derived exosomes miR-221 and miR-214 than the control group （P <0.05）. The PD-N group had significantly higher expression levels of miR-221 and miR-214 than the PD-MCI group and the PD-D group （P <0.05）. The expression levels of miR-221 and miR-214 were negatively correlated with UPDRS score and were positively correlated with MoCA score in PD patients （P <0.05）. The expression level of miR-221 or miR-214 alone or in combination had an area under the ROC curve of 0.700， 0.714， and 0.794， respectively， in predicting cognitive impairment in PD （P <0.05）.Conclusions The expression levels of the serum nerve-derived exosomes miR-221 and miR-214 are downregulated in PD patients and are correlated with the condition of PD and the severity of cognitive impairment. Combined measurement of miR-221 and miR-214 has a certain value in predicting cognitive impairment in PD.