Objective. To evaluate the efficacy and safety of mesalamine in conjunction with probiotics for ulcerative colitis. Methods. Random controlled trials (RCTs) were searched in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP (VIP Database for Chinese Technical Periodicals) from inception to October 2019. Methodological quality was assessed by the Cochrane Collaboration tool. The quality of evidence was rated by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Data analysis was carried out in Review Manager 5.3. Results. A total of fifteen studies met the criteria for inclusion. Thirteen studies reported the clinical efficacy, three studies provided data on the clinical symptom scores, two trials reported disease activity index, four studies evaluated endoscopic score, and twelve studies reported adverse events. For ulcerative colitis (UC), mesalamine and probiotics had better clinical efficacy than mesalamine alone (≤8 weeks: RR = 1.12, 95% CI: 1.07–1.18, P<0.0001; >8 weeks: RR = 1.25, 95% CI: 1.11–1.41, P=0.0003). On the clinical symptom scores, disease activity index, and endoscopic score, UC patients receiving mesalamine and probiotics had significant difference than patients receiving mesalazine alone (MD = −2.02, 95% CI: −3.28 to −0.76, P=0.002; MD = −1.20, 95% CI: −1.76 to −0.65, P<0.001; and MD = −0.42, 95% CI: −0.61 to −0.23, P<0.0001, respectively). There was no statistically significant difference in adverse events between the two groups (RR = 0.88, 95% CI: 0.54 to 1.43, P=0.60). Conclusion. Our meta-analysis results supported that mesalamine and probiotics were effective and safe in treating ulcerative colitis.