OBJECTIVE: Gut dysbiosis has been implicated in the pathogenesis of chronic kidney disease (CKD). Restoring gut microbiota with prebiotic, probiotic, and synbiotic supplementation has emerged as a potential therapeutic intervention but has not been systematically evaluated in the CKD population. DESIGN AND METHODS: This is a systematic review. A structured search of MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and the International Clinical Trials Register Search Portal was conducted for articles published since inception until July 2017. Included studies were randomized controlled trials investigating the effects of prebiotic, probiotic, and/or synbiotic supplementation (>1 week) on uremic toxins, microbiota profile, and clinical and patient-centered outcomes in adults and children with CKD. RESULTS: Sixteen studies investigating 645 adults met the inclusion criteria; 5 investigated prebiotics, 6 probiotics, and 5 synbiotics. The quality of the studies (Grades of Recommendation, Assessment, Development and Evaluation) ranged from moderate to very low. Prebiotic, probiotic, and synbiotic supplementation may have led to little or no difference in serum urea (9 studies, 345 participants: mean difference [MD] -0.30 mmol/L, 95% confidence interval [CI] -2.20 to 1.61, P = .76, I = 53%), indoxyl sulfate (4 studies, 144 participants: MD -0.02 mg/dL, 95% CI -0.09 to 0.05, P = .61, I = 0%), and p-cresyl sulfate (4 studies, 144 participants: MD -0.13 mg/dL, 95% CI -0.41 to 0.15, P = .35, I = 0%). Prebiotic supplementation may have slightly reduced serum urea concentration (4 studies, 105 participants: MD -2.23 mmol/L, 95% CI -3.83 to -0.64, P = .006, I = 11). Of the 2 studies investigating microbiota changes, synbiotic interventions significantly increased Bifidobacterium. Supplement effects on clinical outcomes were uncertain. CONCLUSIONS: There is limited evidence to support the use of prebiotics, probiotics, and/or synbiotics in CKD management.