Water treatment is crucial due to rising water demand across the board, including drinking, agriculture, industry, etc. Pathogens are a type of contamination that must be studied to improve water purification methods. This study investigates the elimination of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) using Clinoptilolite/TiO2/ZnO nanocomposite with varied TiO2/ZnO ratios of 1:1, 1:2, and 2:1 under UVA and UVC light irradiation. To synergize the effect of coupling TiO2 with ZnO, we synthesized nanocomposite Clinoptilolite/TiO2/ZnO to make a powerful system for water and wastewater disinfection. The characterization tests, including X-ray diffraction, field emission scanning electron microscopy, X-ray energy diffraction, Fourier-transform infrared spectroscopy, diffuse reflection spectroscopy, and nitrogen adsorption-desorption, were performed to confirm the structure. The optimum response for bacterial removal was found by using the determination-optimal (D-optimal) design of response surface methodology (RSM). 100% removal was obtained for E. coli and S. aureus under UVA irradiation and contact time of 100 min for both of them.