Introduction While subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa improve motor symptoms in Parkinson disease (PD) to a similar magnitude, their combined effect remains unclear. We sought to evaluate whether STN-DBS and levodopa yield differential effects on motor outcomes, dyskinesia, and activities of daily living (ADL) when combined compared to when administered alone. Methods We conducted a meta-analysis of all studies reporting motor, dyskinesia, and ADL outcomes after bilateral STN-DBS in PD with presurgical Unified Parkinson’s Disease Rating Scale (UPDRS-III) in Medication-OFF and Medication-ON states and postsurgical assessments in four conditions: Stimulation-ON/Medication-ON, Stimulation-ON/Medication-OFF, Stimulation-OFF/Medication-ON, and Stimulation-OFF/Medication-OFF. Dyskinesia duration (UPDRS item 32) and ADL (UPDRS-II) were compared between high and low postsurgical levodopa equivalent daily dose (LEDD) reduction. Random-effects meta-analyses using generic-inverse variance were conducted. Confidence in outcomes effect sizes was assessed. Results Twelve studies were included ( n  = 401 patients). Stimulation-ON/Medication-ON was associated with an UPDRS-III improvement of − 35.7 points 95% confidence interval, − 40.4, − 31.0 compared with Stimulation-OFF/Medication-OFF, − 11.2 points − 14.0, − 8.4 compared with Stimulation-OFF/Medication-ON, and − 9.5 points − 11.0, − 8.0 compared to Stimulation-ON/Medication-OFF within 5 years. The difference was maintained beyond 5 years by − 28.6 − 32.8, − 24.4, − 8.1 − 10.2, − 5.9, and − 8.0 − 10.3, − 5.6, respectively. No difference was observed between Stimulation-ON/Medication-OFF and Stimulation-OFF/Medication-ON within and beyond 5 years. Dyskinesia duration and ADL outcomes were similar in high vs. low postsurgical LEDD reduction. Conclusion Subthalamic nucleus deep brain stimulation and levodopa independently lessened motor severity in PD to a similar magnitude, but their combined effect was greater than either treatment alone, suggesting therapeutic synergism.