Background: In recent years, fusion of nanotechnology and medicine represents one of the major breakthroughs of modern science with the aim of developing nanomaterials for diagnosis, treatment, and overall improving health for the benefit of humankind. Objective: The aim of the study was to synthesize, characterize, and evaluate the antidiabetic effect of zinc oxide nanoparticles (ZnO NPs) from Syzygium cumini (SC). Materials and Methods: ZnO NPs were synthesized using SC seed extract and was characterized by ultraviolet-visible spectroscopy, Fourier transform-infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). Inhibitory potential of the ZnO NPs against α-amylase and α-glucosidase was analyzed in vitro, while AutoDock was used to analyze its potential in silico. Results: The FT-IR analysis suggested that the obtained ZnO NPs have been stabilized through the interactions of phenolic present in the seed extract. XRD pattern analysis confirmed the crystalline nature of the nanoparticles and TEM images revealed the polygonal structure of ZnO NPs of 16.7–22.9 nm in size. Molecular interaction studies of the phenolics from the SC seed extract with α-amylase and α-glucosidase have outlined its high affinity toward it relative to acarbose, while in vitro inhibitory potential studies of the ZnO NPs revealed that it could inhibit the enzymes similar to acarbose. Conclusion: Overall observations imply that phenolics of the SC seed extract helped in synthesis of the NPs and also its role in inhibitory potential which can be used as a potent antidiabetic drug.