BACKGROUND : Cola nitida is amongst the evergreen plants native to West Africa used in the treatment of various ailments including diabetes. OBJECTIVE : This study aims to investigate the antidiabetic effects of the hot water extract of C. nitida seeds in type 2 diabetic rats. METHODS : Type 2 diabetic rats were orally administered with low (150 mg/kg bw) and high (300 mg/kg bw) doses of the hot water extract for 6 wk and thereafter, blood glucose, insulin level, lipid profile, pancreatic β-cell function, perfusion and morphology, redox imbalance, glycolytic and cholinergic enzymes, as well as of caspase-3 and Nrf2 expressions were measured. RESULTS : Treatment with the extract led to significant depletion of blood glucose, serum triglycerides, LDL-cholesterol, fructosamine, ALT, and uric acids, while elevating serum insulin and HDL-cholesterol levels. The infusion also significantly (p < 0.05) elevated GSH level, SOD, catalase, α-amylase, and ATPase activities, with concomitant depletion of myeloperoxidase enzyme activity, and NO and MDA levels in the serum and pancreas. Significantly (p < 0.05) improved pancreatic β-cell function and morphology were observed in rats treated with C. nitida, with restored pancreatic capillary networks. C. nitida inhibited the activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose 6 phosphatase, and acetylcholinesterase while downregulated the Nrf2 expression. NMR analysis of the extract revealed the presence of caffeine and theobromine. The molecular docking studies indicated that identified compounds displayed strong molecular interactions with caspase-3 and Nrf2. CONCLUSIONS : These results insinuate the antidiabetic activities of C. nitida hot water extract and may be attributed to the NMR-identified compounds.