A multimillion-dollar boom is achieved every year by the ethnopharmaceutical companies, creating awareness around the globe to use herbal medicines to stay and live a healthy life. Nearly, two-thirds of the plants were discovered for herbal remedies, and some plants are even endangered to get extinct from the globe for their repeated utility. Sarcostemma brevistigma is one among the undiscovered medicinal plants which belongs to the family Asclepiadaceae found distributed in Indian states of Bihar, Bengal, Konkan, Tamil Nadu, and Kerala. This study was intended to determine the antidiabetic property of plant extract of Sarcostemma brevistigma evidenced by biochemical parameters, antioxidant activity, with the histopathological analysis in diabetic induced mice. Animals that were orally treated with the S. brevistigma extract showed blood glucose lowering effect when compared to the alloxan-induced mice, i.e., from 391.5 ± 6.3 to 193.6 ± 4.3 mg/dL. There is the significant increase in insulin level (P < 0.05) (27.97 ± 1.6 mIU/L) which is comparable to the metformin administered test group (30.35 ± 0.6 mIU/L). A significant difference (P < 0.05) of both ALT and AST levels were observed when compared to the other groups. A significant increase in antioxidant activity (reduced glutathione, malondialdehyde, superoxide dismutase) in plant extract administered group was observed when compared to the other treatment groups. Histopathological studies showed abnormalities in the liver, pancreas, kidney, lungs, heart, and spleen of alloxan-induced diabetic rats. The abnormalities were found to be normalized to a considerable extent after treatment with S. brevistigma extract. The results stood as evidence for S. brevistigma as an active antidiabetic herbal plant. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.