BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that has been increasingly linked to gut-brain axis dysfunction. Fecal microbiota transplantation (FMT), a microbiome-targeted intervention, has shown theoretical and preliminary clinical potential in PD, but randomized clinical evidence remains limited. This review aimed to systematically evaluate the effects of FMT on motor, non-motor, and cognitive outcomes in patients with PD. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review and meta-analysis of randomized controlled trials (RCTs) comparing FMT with placebo or conventional care in PD was conducted. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Pooled analyses were performed using a random-effects model, and the certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Five RCTs involving 226 participants were included. No statistically significant differences were observed between the FMT and control groups in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III, Montreal Cognitive Assessment (MoCA), or Mini-Mental State Examination (MMSE) scores at any assessed follow-up time, with heterogeneity generally low to moderate across outcomes. CONCLUSIONS: Based on current evidence from five small RCTs, FMT did not demonstrate a statistically significant benefit for motor, daily living, or cognitive outcomes in PD. However, these findings should be interpreted cautiously, given the limited sample size, short follow-up duration, and between-study differences in intervention protocols. Larger, well-designed RCTs with standardized FMT protocols and longer follow-up are needed. The PROSPERO Registration: This systematic review was registered in the PROSPERO database under registration number CRD420251121443, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251121443.
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