The ameliorating effect of different fractions of Anonna muricata ethanol leaves extract in oxidative pancreatic injury as well as their antihyperglycemic effect were investigated in vitro and ex vivo. Oxidative pancreatic injury was induced by incubating pancreatic tissue with ferrous sulphate (FeSO₄ )_. The antioxidative potentials of the fractions together with its ability to inhibit carbohydrate digesting enzymes, intestinal glucose absorption, and its ability to modulate muscle glucose uptake were determined. All the fractions significantly scavenge free radicals in dose-dependent manner and increase significantly increase the catalase and superoxide dimutase level thereby ameliorating lipid peroxidation. All the fractions also inihibited glucose digesting enzymes and absorption in dose-dependent manner. Glucose uptake was enhanced by the fractions in isolated psoas muscle of rats. The ethyl acetate fraction showed more potent amelioration and anti-hyperglycemic potentials among all the fractions. This could be further exploited as therapeutic strategy for the management of postprandial hyperglycemia as well as T2D. PRACTICAL APPLICATIONS: Annona muricata is among the edible fruits in the world with reported nutritional as well as medicinal values. The anticancer activity of the leaves and the fruits have been reported. Its ability to inhibit carbohydrate digesting enzymes and absorption and enhancing muscle glucose uptake as well as protection of pancreatic β-cell from oxidative damage further support its reported antidiabetic properties. A. muricata provided a cheap and alternative source of nutraceuticals, which could be further exploited as therapeutic strategy for the treatment of postprandial hyperglycemia in T2D.