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Abstract This study aimed to evaluate the antidiabetic potential of the rind of Punica granatum var. nana. Acute oral toxicity test revealed the safety profile of its ethanolic extract. The extract was administered at 200 mg/kg b.wt to streptozotocin-induced diabetic rats. Serum diagnostic markers of diabetes (insulin, glucose and glycated hemoglobin), inflammatory mediators (tumor necrosis factor-α, interleukin-6, and nitric oxide), and oxidative stress (total antioxidant capacity and reduced glutathione and malondialdehyde) were assayed. The ethanolic extract was further fractionated and assessed for the aforementioned bioactivities at two different doses (100 and 200 mg/kg b.wt). The results revealed that the ethyl acetate fraction of rind exhibited the highest activities. Using different chromatographic techniques, four compounds were isolated and identified as rutin, gallic acid, nictoflorin, and tulipanin. In conclusion: The ethyl acetate fraction of the rind of Punica granatum var. nana may provide a potential therapeutic approach for hyperglycemia. GRAPHICAL ABSTRACT