Abstract This study aimed to evaluate the glymphatic system activity in Parkinson’s disease (PD) with and without rapid eye movement sleep behavior disorder (RBD) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) methods. Overall, 91 patients with PD and 33 healthy controls were recruited. PD patients were divided into PD-RBD (n = 55) and PD-nRBD (n = 36) groups according to RBD scales. The ALPS-index and enlarged perivascular spaces (EPVS) scores were calculated. PD-RBD group exhibited lower ALPS-index than PD-nRBD and controls after controlling for the effect of age (p = 0.018 and p = 0.001). PD-RBD group showed higher UPDRS part I and HAMD score than those in PD-nRBD group. RBD symptom was independently correlated with ALPS-index in PD (β = −0.259, p = 0.014). In conclusion, PD with possible RBD correlated with more severe glymphatic system dysfunction and non-motor symptoms than those in PD without RBD.