Diabetes mellitus is a common metabolic disorder characterized by chronic hyperglycemia, requiring the development of alternative therapies to improve glycemic control. Watermelon rind (Citrullus lanatus (Thunb.) Matsum), usually discarded as waste, contains various bioactive compounds potentially having anti-diabetic benefits. This study aimed to evaluate the antidiabetic potential of watermelon rind extract through a comprehensive approach, including secondary metabolite content profiling, Fourier transform infrared spectroscopy (FTIR) analysis, total flavonoid content determination, molecular docking assay, and in vitro enzyme inhibition assay targeting a-glucosidase. Preliminary phytochemical screening showed the presence of major secondary metabolites such as flavonoids, saponins, and phenolic acids. FTIR analysis confirmed the presence of functional groups typical of these bioactive compounds, including hydroxyl, carbonyl, and aromatic groups. The total flavonoid content was relatively high, indicating significant antioxidant and therapeutic potential. Molecular docking studies were conducted to explore the interaction of bioactive compounds from watermelon rind with a-glucosidase enzyme. The docking results identified a strong binding affinity of specific flavonoids, particularly quercetin derivatives, within the active site of a-glucosidase, indicating a potential inhibitory mechanism. The in vitro assay further validated these findings by showing significant inhibitory activity of watermelon rind extract against a-glucosidase, which plays an important role in carbohydrate digestion and glucose absorption. The results of the in vitro assay aligned with the predictions from molecular docking. These findings suggest that watermelon rind extract has promising antidiabetic potential through a-glucosidase inhibition, supported by the content of flavonoids and other bioactive compounds.