Patients with Parkinson’s disease (PD) may exhibit symptoms of sympathetic dysfunction that can be measured using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. We investigated the relationship between microstructural brain changes and 123I-MIBG uptake in patients with PD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analyses. This retrospective study included 24 patients with PD who underwent 3 T magnetic resonance imaging and 123I-MIBG scintigraphy. They were divided into two groups: 12 MIBG-positive and 12 MIBG-negative cases (10 men and 14 women; age range: 60–81 years, corrected for gender and age). The heart/mediastinum count (H/M) ratio was calculated on anterior planar 123I-MIBG images obtained 4 h post-injection. VBM and DTI were performed to detect structural differences between these two groups. Patients with low H/M ratio had significantly reduced brain volume at the right inferior frontal gyrus (uncorrected p < 0.0001, K > 90). Patients with low H/M ratios also exhibited significantly lower fractional anisotropy than those with high H/M ratios (p < 0.05) at the left anterior thalamic radiation, the left inferior fronto-occipital fasciculus, the left superior longitudinal fasciculus, and the left uncinate fasciculus. VBM and DTI may reveal microstructural changes related to the degree of 123I-MIBG uptake in patients with PD. • Advanced MRI methods may detect brain damage more precisely. • Voxel-based morphometry can detect grey matter changes in Parkinson’s disease. • Diffusion tensor imaging can detect white matter changes in Parkinson’s disease.