Background:Recent studies have discovered that the antiangina agent ranolazine exerts a glucometabolic effect. Objective: This systematic review and meta-analysis aimed to further understand the efficacy and safety profile of ranolazine in patients with diabetes. Methods: Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and EMBASE databases and in ClinicalTrials.gov up to July 2017. Efficacy end points were defined as the change in hemoglobin A(1C) (A1C) and fasting serum glucose (FSG) levels. Safety end points included the incidence of hypoglycemia, persistent hyperglycemia, and major adverse cardiovascular events (MACE). Sensitive and subgroup analyses were also conducted. Results: Seven RCTs with 4461 diabetic patients were selected. Compared with placebo, the use of ranolazine significantly reduced the levels of A1C (weighted mean difference [WMD] = -0.49%; 95% CI = -0.58 to -0.40; P < 0.00001) and FSG (WMD = -6.70 mg/dL; 95% CI = -11.87 to -1.52; P = 0.01). No significant differences were observed in the rates of hypoglycemia (relative risk [RR] = 1.17; 95% CI = 0.76 to 1.80; P = 0.47), persistent hyperglycemia (RR = 0.78; 95% CI = 0.47 to 1.31; P = 0.35), and MACE (RR = 0.65; 95% CI = 0.32 to 1.32; P = 0.23). Conclusion: Ranolazine exerts a positive effect on glucose control and is a well-tolerated agent for patients with diabetes.