ABSTRACT The severe threat of microbial contamination to human life and health safety necessitates urgent research and development of antimicrobial materials capable of inhibiting or eradicating pathogens. Cyclodextrin metal-organic framework (CD-MOF) was utilized as a carrier to encapsulate gold nanoparticles (AuNPs), resulting in a composite material (Au@CD-MOF) that exhibited remarkable antibacterial properties. The antibacterial study revealed that Au@CD-MOF completely eradicated Staphylococcus aureus (S. aureus) and Listeria monocytogenes (L. monocytogenes) at a concentration of approximately 1 × 105 CFU/mL after 48 h and 36 h, respectively. Moreover, Au@CD-MOF also demonstrated the complete elimination of Escherichia coli O157:H7 (E. coli O157:H7), Pseudomonas aeruginosa PAO1 (P. aeruginosa PAO1), and Salmonella typhimurium (S. typhimurium) at a concentration of approximately 1 × 105 CFU/mL after 48 h. Moreover, the antibacterial mechanism of Au@CD-MOF was investigated using E. coli O157:H7 and S. aureus as model organisms. The findings revealed that Au@CD-MOF disrupted the integrity of cell membranes and diminished their potential, consequently impeding the normal functions of the bacteria. Additionally, the heightened permeability of cell membranes induced by Au@CD-MOF resulted in substantial leakage of nucleic acids and proteins, ultimately leading to bacterial eradication.