Human norovirus (HuNoV) threatens human health worldwide, highlighting the critical need for antiviral materials. In this study, copper and zinc nanoparticles (NPs) as inorganic antiviral materials and a cellulose nanofiber (CNF) were selected to construct a hybrid inorganic-organic composite film (CuO/ZnO NPs-CNF) against MS2 and murine norovirus 1 (MNV-1) (surrogates for HuNoV) viruses. Selected NPs concentrations (50µM of CuO NPs and 5mM of ZnO NPs) showed non-toxicity (89.88% of cell viability) through the MTT assay. Upon the development and characterization of the CuO/ZnO NPs-CNF film, high compatibility between CuO/ZnO NPs and CNF was identified, along with consistent thickness, low moisture content, and water solubility. A synergistic antiviral effect was exhibited in vitro and on the film against MS2 and MNV-1 in the mentioned co-treated inorganic matrix within 1h. The antiviral stability of the film was also maintained at various temperatures (-18°C, 5°C, and 25°C) and humidities (20–30%, 50–60%, and 70–80%). When a synergistic antiviral effect was exhibited on the CuO/ZnO NPs-CNF film against both MS2 and MNV-1, mechanisms analysis by SDS-PAGE and RT-qPCR revealed that there were damages to both capsid protein and RdRP. The application of CuO/ZnO NPs-CNF film on clams resulted in a significant decrease in the survival rate of MS2 by up to 65.67% and MNV-1 by up to 78.62% when treated at low temperatures compared to the CNF film. Taken together, these results suggest that the CuO/ZnO NPs-CNF film could be used as potential anti-HuNoV agent in the food industry.