Binary zinc oxide (ZnO) nanocomposites with different noble metals, silver (Ag) and ruthenium (Ru), were prepared from an aqueous leaf extract of Callistemon viminalis. The biosynthesized photocatalysts were characterized and examined for their photocatalytic disinfection against Escherichia coli isolated from hospital wastewater. The influence of the different noble metals showed a difference in physicochemical characteristics and photocatalytic efficiency between Ag-ZnO and Ru-ZnO. The photocatalytic degradation of methylene blue and photocatalytic disinfection were found to be in the order Ag-ZnO > Ru-ZnO > ZnO. The photocatalytic disinfection of Ag-ZnO reached a 75% reduction in 60 min, compared to 34 and 9% reductions of Ru-ZnO and ZnO, respectively. The kinetic reaction rate for the photocatalytic disinfection of Ag-ZnO was found to be 2.8 times higher than that of Ru-ZnO. The outstanding photocatalytic activity of Ag-ZnO over Ru-ZnO was attributed to higher crystallinity, greater UVA adsorption capacity, smaller particle size, and the additional antimicrobial effect of Ag itself. The C. viminalis-mediated Ag-ZnO nanocomposites can be a potential candidate for photocatalytic disinfection of drug-resistant E. coli in hospital wastewater.