Abstract Background This study was performed to evaluate the clinical effectiveness of alternative strategies for the prevention and treatment of patients with chronic kidney disease undergoing peritoneal dialysis and colonized by Staphylococcus aureus. Methods A systematic review and meta-analysis were performed. The literature search involved the following databases: the Cochrane Controlled Trials Register, Embase, LILACS, CINAHL, SciELO, and PubMed/Medline. The descriptors were “Staphylococcus aureus,” “MRSA,” “MSSA,” “treatment,” “decolonization,” “nasal carrier,” “colonization,” “chronic kidney disease,” “dialysis,” and “peritoneal dialysis.” Randomized controlled trials that exhibited agreement among reviewers as shown by a kappa value of >0.80 were included in the study; methodological quality was evaluated using the STROBE statement. Patients who received various antibiotic treatments (antibiotic group) or topical mupirocin (mupirocin group) were compared with those who received either no treatment or placebo (control group). Patients in the antibiotic group were also compared with those in the mupirocin group. Results In total, nine studies involving 839 patients were included in the analysis, 187 (22.3 %) of whom were nasal carriers of S. aureus. The probability of S. aureus infection at the catheter site for peritoneal dialysis was 74 % lower in the mupirocin than control group (odds ratio [OR], 0.26; 95 % confidence interval [CI], 0.14–0.46; p