This study proposed to detect changes in brain microstructure in patients with Parkinson's disease (PD) using diffusion kurtosis imaging (DKI) to quantitatively diagnose early-stage PD. Conventional magnetic resonance imaging and DKI scanning were performed in 24 patients with PD and in 12 age- and sex-matched healthy participants. Hoehn and Yahr (H–Y) stage and Unified Parkinson's Disease Rating Scale-III (UPDRS-III) scores were obtained from both groups. The mean kurtosis (MK), axial kurtosis, and radial kurtosis of the bilateral substantia nigra on DKI were measured and compared between the two groups. The correlations between MK, H–Y stage, and UPDRS-III scores were determined. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of MK for PD in the substantia nigra. The MK value in the PD group was 0.971. The area under the ROC curve of the substantia nigra was 0.905; the sensitivity and specificity were 0.917 and 0.875, respectively, and the cutoff value was 1.046. The MK of the substantia nigra in the PD group had no significant correlation with the H–Y stages but was negatively correlated with the UPDRS-III scores (r = − 0. 5 0 6 ; p = 0. 0 1 2). Our research identified DKI as a novel tool for the qualitative diagnosis of PD. The optimal MK value for PD diagnosis could be determined with ROC analysis. [ABSTRACT FROM AUTHOR]