In this study, a variety of nanocomposites, namely, MEL@AgNPs, MEL@ZnONPs, and Ag–ZnO/MEL/GA were biosynthesized using MEL and gum arabic to serve in biomedical applications. The synthesized nanocomposites were examined using X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and FTIR spectroscopy. The physicochemical properties and biomedical activities of the synthesized nanocomposites were investigated. The Ag–ZnO/MEL/GA nanocomposites showed greater antidiabetic activity against α-amylase and α-glucosidase, and higher antibacterial activity compared to MEL@AgNPs and MEL@ZnONPs. Furthermore, HepG2 cells were exposed to MEL@AgNPs, MEL@ZnONPs, and Ag–ZnO/MEL/GA nanocomposites for 24 h and their IC₅₀ values were 63.25, 26.91 and 28.97 μg mL⁻¹ (P < 0.05), respectively. According to this comparative study, it is apparent that the Ag–ZnO/MEL/GA nanocomposites have a great potential to serve as antitumor agents against HepG2, and antidiabetic and antibacterial agents.