The glymphatic system is crucial for clearing metabolic waste from the brain, maintaining neural health and cognitive function. This study explores the glymphatic system's role in Moyamoya disease (MMD), characterized by progressive cerebral artery stenosis and brain structural lesions. We assessed 33 MMD patients and 21 healthy controls using diffusion tensor imaging along the perivascular space (DTI-ALPS) and global cortical gray matter-cerebrospinal fluid (CSF) coupling indices (gBOLD-CSF), which are indirect measurements of the glymphatic system. Cerebral perfusion in patients was evaluated via computed tomography perfusion imaging. We also measured the peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity (WMH) burden, and cognitive function. MMD patients exhibited lower ALPS and gBOLD-CSF coupling indices compared to controls (P < 0.01), indicating disrupted glymphatic function. Significant cognitive impairment was also observed in MMD patients (P < 0.01). ALPS indices varied with cerebral perfusion stages, being higher in earlier ischemic stages (P < 0.05). Analysis of brain structure showed increased CSF volume, PSMD index, and higher WMH burden in MMD patients (P < 0.01). The ALPS index positively correlated with white matter volume and cognitive scores, and negatively correlated with CSF volume, PSMD, and WMH burden (P < 0.05). Mediation analysis revealed the number of periventricular WMH significantly mediated the relationship between glymphatic dysfunction and cognitive impairment. In summary, MMD patients exhibit significant glymphatic system impairments, associated with brain structural changes and cognitive deficits.