In this study, zinc oxide (ZnO) nanoparticles were prepared and modified using a wet chemical method with different concentrations of Ag and Cu nanoparticles. The objective was to improve the mechanical, optical, and antibacterial properties of the coated paper by using the prepared pigments. The long-term antimicrobial effects of the coated paper were evaluated over 25 years. The successful synthesis of a hexagonal structure of ZnO nanoparticles decorated with spherical Ag and Cu nanoparticles ranging from 20 to 50 nm was confirmed using X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and transmission electron microscopy (TEM). By increasing the concentrations of Ag and Cu from 0.01% to 1.0%, the mechanical properties of the coated paper were enhanced. The tensile strength reached a maximum of 6.77 kN/m and 7.03 kN/m, elongation increased to 1.69% and 1.70%, tensile energy absorption improved to approximately 77 and 80 J/m2, and burst strength rose to 218 and 219 kPa, respectively. The use of Ag-modified ZnO maintains the optical properties, while Cu-modified ZnO reduces brightness and whiteness without affecting opacity. The antimicrobial inhibition activity was improved with higher silver (Ag) and copper (Cu) content. The formulations containing 1% Ag/ZnO and 1%Cu/ZnO showed long-lasting antibacterial effects against gram-positive Staphylococcus aureus bacteria. Even after 25 years of aging, they maintained inhibition rates of 92.2% and 62.2%, respectively. The molecular docking and GeneMANIA analysis revealed the potential of ZnO, Ag-modified ZnO, and Cu-modified ZnO nanoparticles to disrupt the S. aureus cell wall biosynthesis pathway by targeting the MurA enzyme and associated cell wall synthesis genes.