Parkinson's disease (PD) is a degenerative disorder that affects the central nervous system. PD-related alterations in structural and functional neuroimaging have not been fully explored. This study explored multi-modal PD neuroimaging and its application for predicting clinical scores on the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Multi-modal imaging that combined 123I-Ioflupane single-photon emission computed tomography (SPECT) and diffusion tensor imaging (DTI) were adopted to incorporate complementary brain imaging information. SPECT and DTI images of normal controls (NC; n = 45) and PD patients (n = 45) were obtained from a database. The specific binding ratio (SBR) was calculated from SPECT. Tractography was performed using DTI. Group-wise differences between NC and PD patients were quantified using SBR of SPECT and structural connectivity of DTI for regions of interest (ROIs) related to PD. MDS-UPDRS scores were predicted using multi-modal imaging features in a partial least-squares regression framework. Three regions and four connections within the cortico-basal ganglia thalamocortical circuit were identified using SBR and DTI, respectively. Predicted MDS-UPDRS scores using identified regions and connections and actual MDS-UPDRS scores showed a meaningful correlation (r = 0.6854, p < 0.001). Our study provided insight on regions and connections that are instrumental in PD.