Positron emission tomography/computed tomography (PET/CT) is a molecular imaging method commonly used to diagnose and differentiate Parkinson’s disease (PD). This study aimed to evaluate the performance of PET/CT with ¹¹C-2β-Carbomethoxy-3β-(4-fluorophenyl) tropane (¹¹C-CFT) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) tracers in the differential diagnosis between PD, multiple system atrophy parkinsonian type (MSA-P), progressive supranuclear palsy (PSP) and vascular parkinsonism (VP) using the data of 220 patients with clinical PD-like symptoms. Of the 220 enrolled patients, 166 (PD, n = 80; MSA-P, n = 54; PSP, n = 15; VP, n = 17) completed the motor, cognitive and PET/CT assessment and were included in this study. ¹¹C-CFT and ¹⁸F-FDG PET/CT images were analyzed using the SNBPI toolbox and CortexID Suite software. The uptake values of ¹¹C-CFT and ¹⁸F-FDG PET/CT were compared among the groups after controlling for covariates using generalized linear models. Receiver operating characteristic (ROC) curves were generated to estimate the diagnostic values. Patients with PSP showed the most significant reduction on ¹¹C-CFT PET/CT, while patients with PD and MSA-P showed similar reductions, and patients with VP did not show any significant reduction in ¹¹C-CFT uptake. The areas under the curve (AUCs) for ¹¹C-CFT PET/CT for distinguishing PD from VP, PSP, and MSA-P were 0.902, 0.830, and 0.580, respectively, and 0.728 for distinguishing advanced-stage PD from PSP. On ¹⁸F-FDG PET/CT, the AUCs for distinguishing PD from PSP and MSA-P were 0.968 and 0.963, respectively. These results suggest that ¹¹C-CFT and ¹⁸F-FDG PET/CT complement each other in improving the accuracy in differential diagnosis of PD.