The rise of antibiotic-resistant bacterial infections has become a major global health issue. To combat multidrug-resistant (MDR) bacteria, there is a growing need for innovative antimicrobial materials. Metal nanoparticles (MNPs), especially multi-metallic nanoparticles (MMNPs), show great potential in this regard. MMNPs, composed of multiple metals, have unique physicochemical properties and excellent biocompatibility, contributing to their strong antimicrobial activity. These nanoparticles can disrupt bacterial cell membranes, release metal ions, damage biomolecules, generate reactive oxygen species (ROS), cause protein dysfunction, and damage DNA. This review summarizes and compares research on the antibacterial activities of MMNPs and their synergistic effects. It also explains the mechanisms through which MMNPs exert their antibacterial effects. Recent advances in MMNPs that help overcome antibacterial resistance are emphasized. The physicochemical and multifunctional properties of MMNPs are crucial in determining their effectiveness against bacterial infections. By integrating current knowledge on the antibacterial activities of MMNPs, this review provides valuable insights into their potential applications in combating bacterial infections. Keywords: Infectious diseases · Antibiotics · Antibacterial materials · Synergistic effect · Multi-drug resistance · Multimetallic nanoparticles · Antibacterial activity.The rise of antibiotic-resistant bacterial infections has become a major global health issue. To combat multidrug-resistant (MDR) bacteria, there is a growing need for innovative antimicrobial materials. Metal nanoparticles (MNPs), especially multi-metallic nanoparticles (MMNPs), show great potential in this regard. MMNPs, composed of multiple metals, have unique physicochemical properties and excellent biocompatibility, contributing to their strong antimicrobial activity. These nanoparticles can disrupt bacterial cell membranes, release metal ions, damage biomolecules, generate reactive oxygen species (ROS), cause protein dysfunction, and damage DNA. This review summarizes and compares research on the antibacterial activities of MMNPs and their synergistic effects. It also explains the mechanisms through which MMNPs exert their antibacterial effects. Recent advances in MMNPs that help overcome antibacterial resistance are emphasized. The physicochemical and multifunctional properties of MMNPs are crucial in determining their effectiveness against bacterial infections. By integrating current knowledge on the antibacterial activities of MMNPs, this review provides valuable insights into their potential applications in combating bacterial infections. Keywords: Infectious diseases · Antibiotics · Antibacterial materials · Synergistic effect · Multi-drug resistance · Multimetallic nanoparticles · Antibacterial activity.