Background: Drug therapy is important for controlling symptoms in Parkinson’s disease (PD). However, it often results in complex medication regimens and could easily lead to drug related problems (DRP), suboptimal adherence and reduced treatment efficacy. A structured medication review (SMR) could address these issues and optimize therapy, although little is known about clinical effects in PD patients. Objective: To analyze whether an SMR improves quality of life (QoL) in PD. Methods: In this multicenter randomized controlled trial, half of the 202 PD patients with polypharmacy received a community pharmacist-led SMR. The control group received usual care. Assessments at baseline, and after three and six months comprised six validated questionnaires. Primary outcome was PD specific QoL [(PDQ-39; range 0 (best QoL) – 100 (worst QoL)]. Secondary outcomes were disability score, non-motor symptoms, general health status, and personal care giver’s QoL. Furthermore, DRPs, proposed interventions, and implemented modifications in medication schedules were analyzed. Results: No improvement in QoL was seen six months after an SMR, with a non-significant treatment effect difference of 2.09 (–0.63;4.80) in favor of the control group. No differences were found in secondary outcomes. In total, 260 potential DRPs were identified (2.6 (±1.8) per patient), of which 62% led to drug therapy optimization. Conclusion: In the current setting, a community pharmacist-led SMR did not improve QoL in PD patients, nor improved other pre-specified outcomes.