Ethanopharmacological Relevance: Swietenia mahagoni (L.) Jacq. is a medicinal plant used in various medicinal practices for the treatment of various human ailments. Materials and Methods: The present study evaluates the antidiabetic potential of Swietenia mahagoni aueous extract (MAE) in fructose-induced diabetic rats with insulin resistance. MAE was analyzed using high-performance liquid chromatography (HPLC) and liquid chromatography mass spectrometry (LCMS) for the identification of constituent bio-actives present. Results: MAE treatment improved glucose levels, reduced the insulin resistance, improved glucose tolerance, improved pancreatic β-cell health, decreased glycated hemoglobin content, reduced lipid peroxides, and improved glycogen content and the activity of enzymes involved in the synthesis of glycogen in the liver. There was also overall improvement in the antioxidant status of the treated groups when compared with that of the diabetic control. The treatment also improved the lipid profile of diabetic rats. The HPLC analysis indicated the presence of gallic acid, scopoletin, coumarin, epicatechin, and ellagic acid, and their presence was confirmed by LCMS analysis. Conclusion: Results supported the antidiabetic potential of MAE in animal model where it can act on multitargets and ameliorate the overall diabetic condition rather targeting to control hyperglycemia. Thus, the study supports the scope of Swietenia mahagoni as an adjuvant in type 2 diabetic patients.