A key feature of Parkinson’s disease (PD) is the depletion of striatal dopamine, which is associated with the motor and non-motor symptoms of the disease. In this study, we sought to investigate the role of dopamine in spatial memory in PD patients in a cross-over medication ON/OFF design. We used a virtual reality task to assess striatal- and hippocampal-dependent spatial memory. Results show that PD patients and age-matched controls rely more on striatal cue-based spatial learning than the young adults tested in previous studies. Medication improved striatal-dependent spatial memory. The benefit of medication on hippocampal-dependent spatial memory depended on prior experience with the task. These findings shed new light on dopaminergic modulation of hippocampal-striatal functions in PD.