Colorectal cancer (CRC) is highly prevalent worldwide and is a leading cause of cancer-related death. Probiotics, prebiotics, and synbiotics have recently attracted attention as preventive measures against colorectal neoplasms. We aimed to analyze the findings of randomized controlled trials (RCTs) on the effects of probiotics, prebiotics, and synbiotics in patients at a high risk of CRC, outlining the challenges and future prospects of using probiotics to prevent colorectal tumors and providing evidence for clinical physicians in particular. PubMed, EMBASE, and the Cochrane Library databases were searched for relevant studies published up to January 7, 2022. RCTs conducted on populations with a high risk of CRC who received probiotics, prebiotics or synbiotics in comparisonwith placebo, candidate agent or no treatment were included. The primary outcome was the incidence or recurrence of any colorectal neoplasms. Additional outcomes included their effects on the diversity of gut microbiota and relevant inflammatory biomarkers. Safety outcomes were also analyzed. Two authors independently screened and selected studies based on pre-specified eligible criteria, performed data extraction and risk-of-bias assessment independently. Nine RCTs were included in the systematic review and meta-analysis. Probiotic supplementation significantly reduced adenoma incidence, but no significant benefit was observed in CRC incidence. Additionally, probiotics modulated gut microbiota and inflammatory biomarkers. Probiotics may have beneficial effects in the prevention of CRC. More RCTs with larger sample sizes are warranted to further confirm these findings.