Gut microbiome has strongly emerged as a pivotal factor in the pathogenesis of stroke via gut-brain axis. However, it remains uncertain whether interventions that modulate gut microbiome can constitute a potent strategy to improve stroke outcome. The present study was carried out to explore interventions that affect stroke outcome through gut-brain axis.Eligibility criteria was applied base on PICO to search and select studies. Appropriate MESH-terms were used as search terms to source for information from PubMed, Web of Science, Cochrane Library, Ebsco, and Scopus from 1st January 1990 to 31st December 2022. Grey literature and secondary references were also considered.The study included 42 studies (39 experimental animal and 3 human clinical researches) with 33 different interventions from the cumulative of 24108 identified studies. These interventions were grouped into 6 different sub groups and and meta-analyzed. There were significant positive effects on stroke with treatment categories of traditional Chinese medicine treatment (SMD = -1.96, 95% CI -2.86 to -1.07), bacteriotherapy based interventions (SMD = -1.38, 95% CI -2.06 to -0.70), synthetic chemicals/drugs (SMD = -2.03, 95% CI -2.99 to -1.06), except with natural product (SMD = -0.52, 95% CI -0.94 to -0.11). Overall, experimental animal (SMD = -1.35, 95% CI -1.78 to -0.93) studies showed significant positive effect on stroke, but overall human clinical (SMD = 0.39, 95% CI -0.53 to 1.32) studies showed no significant positive effect.The present study found diverse categories of microbiome-based interventions that modulate stroke outcome via gut-brain axis. PROSPERO ID: CRD42021281950/CRD42021284426.