Zinc oxide (ZnO) nanoparticles exhibit strong antibacterial activity against Campylobacter jejuni, a leading cause of foodborne illness. The minimum inhibitory concentration (MIC) of ZnO nanoparticles for C. jejuni was determined to be 0.05 to 0.025 mg/ml, which is 8- to 16-fold lower than that for other foodborne pathogens like Salmonella enterica serovar Enteritidis and Escherichia coli O157:H7. ZnO nanoparticles were found to be bactericidal, not bacteriostatic, causing significant morphological changes in C. jejuni cells, transforming them from spiral to coccoid forms. These changes were associated with increased membrane leakage and oxidative stress. Gene expression analysis revealed that oxidative stress genes (katA and ahpC) and a general stress response gene (dnaK) were significantly upregulated in response to ZnO nanoparticles. The antibacterial mechanism of ZnO nanoparticles is likely due to disruption of the cell membrane and oxidative stress in C. jejuni. ZnO nanoparticles are effective at killing C. jejuni even at low concentrations, with a lethal effect observed at 0.03 mg/ml. The study also compared the effectiveness of ZnO nanoparticles against other foodborne pathogens, showing that higher concentrations were required to achieve similar results. The results suggest that ZnO nanoparticles have a broad spectrum of antibacterial activity and could be a promising tool for food safety interventions. The study highlights the importance of understanding the mechanism of action of ZnO nanoparticles to develop safe and effective antimicrobial agents.Zinc oxide (ZnO) nanoparticles exhibit strong antibacterial activity against Campylobacter jejuni, a leading cause of foodborne illness. The minimum inhibitory concentration (MIC) of ZnO nanoparticles for C. jejuni was determined to be 0.05 to 0.025 mg/ml, which is 8- to 16-fold lower than that for other foodborne pathogens like Salmonella enterica serovar Enteritidis and Escherichia coli O157:H7. ZnO nanoparticles were found to be bactericidal, not bacteriostatic, causing significant morphological changes in C. jejuni cells, transforming them from spiral to coccoid forms. These changes were associated with increased membrane leakage and oxidative stress. Gene expression analysis revealed that oxidative stress genes (katA and ahpC) and a general stress response gene (dnaK) were significantly upregulated in response to ZnO nanoparticles. The antibacterial mechanism of ZnO nanoparticles is likely due to disruption of the cell membrane and oxidative stress in C. jejuni. ZnO nanoparticles are effective at killing C. jejuni even at low concentrations, with a lethal effect observed at 0.03 mg/ml. The study also compared the effectiveness of ZnO nanoparticles against other foodborne pathogens, showing that higher concentrations were required to achieve similar results. The results suggest that ZnO nanoparticles have a broad spectrum of antibacterial activity and could be a promising tool for food safety interventions. The study highlights the importance of understanding the mechanism of action of ZnO nanoparticles to develop safe and effective antimicrobial agents.