Although mangiferin has a number of documented beneficial effects, there are no systematic reviews or meta-analyses of its effects in diabetic animal models. To investigate the effects of oral administration of mangiferin on blood glucose levels, body weight, and total cholesterol (TC) and triglycerides (TG) levels in diabetic animal models, a meta-analysis was conducted and the underlying mechanisms were reviewed. Studies from six databases (PubMed, Web of Science, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure), and Wanfang Med) were searched from inception to April 2020. After article screening, a total of 19 articles were included in this meta-analysis. The meta-analysis was performed using RevMan 5.3 and STATA 14.0 software. The overall pooled estimate of standardized mean difference (SMD) of mangiferin's effect on blood glucose was -1.27 [95% confidence interval (CI): -1.71, -0.82, P<0.00001]. Body weight increased in lean diabetic animals with an SMD of 1.41 (95% CI: 0.57, 2.25; P=0.001), while it decreased in obese diabetic animals with an SMD of -0.92 (95% CI: -1.69, -0.14; P=0.02). Mangiferin intake reduced serum TC and TG levels with SMDs of -1.02 (95% CI: -1.43, -0.61; P<0.001) and -1.24 (95% CI: -1.70, -0.79; P<0.001), respectively. The meta-analysis suggests that oral intake of mangiferin has a significant anti-diabetic effect in animal models, and the systematic review suggested that this function might be attributed to its anti-inflammatory and anti-oxidative properties, as well as to its function of improving glucolipid metabolism and enhancing insulin signaling.