Diabetes mellitus has the probability to impair the anastomotic healing and cause postesophagectomy anastomotic leakages but previous studies showed controversial results. This review aims to summary the impact of diabetes mellitus on the risk of anastomotic leakage after esophagectomy. We searched the PubMed and EMBASE databases to recognize English articles that met our eligibility criteria. Odds ratio with 95% confidence interval serves as the appropriate summarized statistic. Sensitivity analysis, meta-regression analysis, and publication bias tests were also performed to perceive potential bias risks. Finally, 16 observational studies with 12359 surgical patients were included. An overall analysis identified that diabetes mellitus was significantly associated with the risk of anastomotic leakage after esophagectomy (odds ratio = 1.63; 95% confidence interval = 1.25-2.12; P < 0.001). Further subgroup analysis showed a significant impact of diabetes mellitus in surgical populations from the Europe and America (odds ratio = 1.42; 95% confidence interval = 1.22-1.65; P < 0.001) but not in the Asian populations (odds ratio = 2.27; 95% confidence interval = 0.86-6.05; P = 0.1). The robustness of these estimates was confirmed by meta-regression analysis and sensitivity analysis. No significant publication bias exists between studies. In conclusion, this systematic review demonstrates that diabetes mellitus can be a significant risk factor of anastomotic leakage for patients undergoing esophagectomy. Our findings need to be further confirmed and modified by more well-designed worldwide multivariable analyses in the future.