Enhancing the antibacterial properties of polymethyl methacrylate (PMMA) dental resins is crucial in preventing secondary infections following dental procedures. Despite the necessity for such improvement, a universally applicable method for augmenting the antibacterial properties of PMMA without compromising its mechanical properties and cytotoxicity remains elusive. Consequently, this study aims to address the aforementioned challenges by developing and implementing a composite material known as zinc oxide/graphene oxide (ZnO/GO) nanocomposites, to modify the PMMA. ZnO/GO nanocomposites were successfully synthesized by a one-step procedure and fully characterized by TEM, EDS, FTIR and XRD. Then the physical and mechanical properties of PMMA modified by ZnO/GO nanocomposites were evaluated through water absorption and solubility test, contact angle test, three-point bending tests, and compression test. Furthermore, the biologicalproperties of the modified PMMA were evaluated by direct microscopic colony count method, crystal violet staining and CCK-8. The results revealed that ZnO/GO nanocomposites were successfully constructed. When the concentration of nanocomposites in PMMA was 0.2 wt. %, the flexural strength of the resin was increased by 23.4%, the compressive strength was increased by 31.1%, and the number of bacterial colonies was reduced by 60.33%. Meanwhile, It was found that the aging of the resin did not affect its antibacterial properties, and CCK-8 revealed that the modified PMMA had no cytotoxicity. ZnO/GO nanocomposites effectively improved the antibacterial properties of PMMA. Moreover, the mechanical properties of the resin were improved by adding ZnO/GO nanocomposites at a lower range of concentrations.