This review discusses the synthesis, characterization, surface modification, antibacterial properties, food packaging applications, and toxicological implications of copper oxide (CuO) nanofillers integrated in films and composites. CuO nanoparticles (NPs) have attracted attention due to their unique physicochemical properties and semiconductor characteristics. Doping CuO NPs with functional materials and functionalizing them with natural or synthetic moieties enhances their antibacterial efficacy in food packaging. The bactericidal effect of modified CuO NPs against foodborne pathogens makes them suitable for food packaging technology. However, the development of effective antimicrobial CuO nanofillers with minimal adverse effects is essential. The review highlights the synthesis methods of CuO NPs, including laser ablation, hydrothermal, microwave irradiation, sonication, and chemical/biogenic reduction. The size, shape, surface chemistry, and dosage of CuO NPs significantly influence their antibacterial activity. CuO NPs can be integrated into polymeric matrices to improve mechanical and antimicrobial properties. CuO-based nanocomposites have been used in food packaging to extend shelf life and prevent microbial contamination. The integration of CuO NPs with other nanomaterials, polymers, and biomacromolecules enhances their properties and efficiency. CuO NPs have been shown to inhibit bacterial growth by disrupting cell membranes, generating reactive oxygen species, and releasing Cu²+ ions. However, the use of CuO NPs must be carefully regulated to avoid toxicity and environmental risks. The migration of CuO NPs into food products is a concern, and simulation models are used to assess their migration and potential health effects. The toxicological implications of CuO NPs depend on their physicochemical properties, such as dissolution, aggregation, stability, and reactivity. CuO NPs can cause toxicity in organisms and affect the environment. The biocompatibility of CuO NPs is also important, and studies have shown that CuO NPs can be toxic to human cells. The review concludes that CuO nanofillers have significant potential in food packaging applications but require further research to address their toxicological and environmental risks. Future studies should focus on eco-friendly synthesis methods and the development of biodegradable alternatives. The integration of CuO nanofillers into food packaging systems could lead to innovative and sustainable packaging solutions.This review discusses the synthesis, characterization, surface modification, antibacterial properties, food packaging applications, and toxicological implications of copper oxide (CuO) nanofillers integrated in films and composites. CuO nanoparticles (NPs) have attracted attention due to their unique physicochemical properties and semiconductor characteristics. Doping CuO NPs with functional materials and functionalizing them with natural or synthetic moieties enhances their antibacterial efficacy in food packaging. The bactericidal effect of modified CuO NPs against foodborne pathogens makes them suitable for food packaging technology. However, the development of effective antimicrobial CuO nanofillers with minimal adverse effects is essential. The review highlights the synthesis methods of CuO NPs, including laser ablation, hydrothermal, microwave irradiation, sonication, and chemical/biogenic reduction. The size, shape, surface chemistry, and dosage of CuO NPs significantly influence their antibacterial activity. CuO NPs can be integrated into polymeric matrices to improve mechanical and antimicrobial properties. CuO-based nanocomposites have been used in food packaging to extend shelf life and prevent microbial contamination. The integration of CuO NPs with other nanomaterials, polymers, and biomacromolecules enhances their properties and efficiency. CuO NPs have been shown to inhibit bacterial growth by disrupting cell membranes, generating reactive oxygen species, and releasing Cu²+ ions. However, the use of CuO NPs must be carefully regulated to avoid toxicity and environmental risks. The migration of CuO NPs into food products is a concern, and simulation models are used to assess their migration and potential health effects. The toxicological implications of CuO NPs depend on their physicochemical properties, such as dissolution, aggregation, stability, and reactivity. CuO NPs can cause toxicity in organisms and affect the environment. The biocompatibility of CuO NPs is also important, and studies have shown that CuO NPs can be toxic to human cells. The review concludes that CuO nanofillers have significant potential in food packaging applications but require further research to address their toxicological and environmental risks. Future studies should focus on eco-friendly synthesis methods and the development of biodegradable alternatives. The integration of CuO nanofillers into food packaging systems could lead to innovative and sustainable packaging solutions.