Mangifera indica (Anacardiaceae family) is renowned for its diverse pharmacological properties, encompassing antidiabetic, antioxidant, and anti-inflammatory effects. The present study delves into the insulin-releasing and glucose-lowering potential of the ethanolic extract of Mangifera indica (EEMI) leaves in streptozotocin-induced type 2 diabetic (STZ-T2D) rats, concurrently investigating its phytoconstituents. EEMI’s effects on insulin secretion were measured using BRIN BD11 β-cells and isolated mouse islets. Its enzymatic inhibitory properties on carbohydrate digestion, and absorption, and free radicals were investigated using in vitro methods. In vivo parameters including the lipid profile and liver glycogen content were assessed in STZ-T2D rats. EEMI exhibited a dose-dependent increase in insulin secretion from clonal pancreatic BRIN BD11 β-cells and isolated mouse islets. EEMI inhibited starch digestion, glucose diffusion over time, and DPPH activity in vitro. In acute in vivo studies, EEMI improved food intake and oral glucose tolerance. Moreover, following 28 days of treatment with EEMI, a remarkable amelioration in body weight, fasting blood glucose, plasma insulin, liver glycogen content, total cholesterol, triglyceride, LDL, VLDL, and HDL levels was observed. Further phytochemical analysis with EEMI identified the presence of alkaloids, tannins, saponins, steroids, and flavonoids. The synergistic effects of EEMI, potentially attributable to naturally occurring phytoconstituents, hold promise for the development of enriched antidiabetic therapies, offering a promising avenue for the management of type 2 diabetes.