Cancer and diabetes represent significant challenges in the field of biomedicine, with major and global impacts on public health. , commonly called 'gum arabic tree,' is recognized for its unique biomedical properties. The current study aimed to investigate the pharmacological potential of -based zinc-oxide nanoparticles (ZnO-NPs) in comparison to the ethanol and methanol-based extracts against cancer, diabetes, and oxidative stress. Green synthesis of ZnO-NPs was performed using barks of . Different techniques for the characterization of ZnO-NPs, including UV-Visible spectroscopy, Scanning Electron Microscopy, Fourier Transmission Infrared (FT-IR) spectroscopy, and X-ray Diffraction (XRD), were utilized. The morphological analysis of ZnO-NPs revealed that the fine NPs have mean particle sizes of 15 ± 1.5 nm. For the solvent based-extraction, leaves and barks were utilized and dissolved into ethanol and methanol for further processing. The MTT assay revealed that the optimum concentration of ZnO-NPs to inhibit the proliferation of liver cancer cell line HepG2 was 100 μg/mL where 67.0 % inhibition was observed; and both ethanol- and methanol-based extracts showed optimum inhibition at 100 μg/mL. The DPPH assay further demonstrated that 250 μg/mL of ZnO-NPs and 1000 μg/mL of both ethanol- and methanol-based extracts, as the optimum concentration for antioxidant activity (with 73.1 %, 68.9 % and 68.2 % inhibition respectively). The α-Glucosidase inhibition assay revealed that 250 μg/mL of ZnO-NPs and 10 μg/mL of both ethanol- and methanol-based extracts as the optimum concentration for antidiabetic activity (with 95 %, 93.7 % and 93.4 % inhibition respectively). The study provided interesting insights into the efficacy and reliability of ZnO-NPs for potential pharmacological application. Further research should be focused on examining specific pathways and the safety of ZnO-NPs in comparison to solvent-based extracts.