The chronic type-2 diabetes mellitus leads to diabetic nephropathy, which is one of the major microvascular complication of end stage renal disease worldwide and causes premature death in diabetic patients. The objective of the present investigation was to evaluate the antidiabetic activity and protective effect of diabetic induced nephropathy of ethanolic extract of seeds of Eugenia jambolana (SEEJ) by using in-vitro and in-vivo models. The in-vitro antidiabetic effect was studied by glucose uptake assay in lymphocyte culture preparation. The in-vivo antidiabetic activity and the effect on diabetic nephropathy was evaluated using streptozotocin-nicotinamide induced type-2 diabetes mellitus in male albino Wistar rats. The results of in-vitro study revealed that SEEJ increased the percentage glucose uptake when calculated in comparison with control group. The in-vivo study showed that blood glucose level was significantly reduced in dose dependent manner when compared to the diabetic control group. In addition, it significantly restored the body weight loss, increased kidney weight, glycosylated haemoglobin, blood urea, blood uric acid, blood urea nitrogen, blood creatinine, urine volume and urine microalbumin levels when compared to diabetic control groups. The report of histopathological study of rat kidney tissues strongly supported the protective effect of SEEJ in diabetic nephropathy. The findings of this investigation concluded that SEEJ has significant antidiabetic activity and potential protective effect in diabetic nephropathy.