Metal-based nanoparticles have been extensively studied for biomedical applications, particularly as antimicrobial agents. These nanoparticles are effective against priority pathogens and have non-specific bacterial toxicity mechanisms, making them less prone to resistance development and broadening their antibacterial activity. This review provides a comprehensive overview of the most relevant types of metal nanoparticles used as antimicrobial agents, including gold (AuNPs), silver (AgNPs), copper oxide (CuONPs), and zinc oxide (ZnONPs). The review emphasizes the comparative discussion of their production methods, physicochemical properties, pharmacokinetics, and toxicological risks. The focus is on their potential as alternatives to traditional antibiotics, especially for combating multi-resistant Gram-negative bacteria. The review highlights the mechanisms of action of metal-based nanoparticles, including their ability to interact with bacterial cell surfaces, destabilize cell walls and membranes, induce oxidative stress, and modulate signal transduction pathways. The synthesis methods of metal and metal oxide nanoparticles include chemical reduction, biochemical, electrochemical, wave-assisted, and cementation methods. Each method has its advantages and challenges, with chemical reduction being the most widely used. Silver nanoparticles (AgNPs) are among the most studied metal-based nanoparticles due to their broad antibacterial activity. They are synthesized through various methods, including conventional chemistry, green chemistry, and biological methods. AgNPs are characterized using techniques such as UV-Vis spectrophotometry, X-ray diffractometry (XRD), transmission electron microscopy (TEM), and infrared spectroscopy (IR). Their pharmacokinetics, absorption, distribution, metabolism, and excretion are influenced by factors such as dose, administration route, and species. AgNPs exhibit antimicrobial activity through mechanisms such as adhesion to bacterial surfaces, destabilization of cell walls and membranes, induction of oxidative stress, and modulation of signal transduction pathways. They also show potential in other biomedical applications, including antifungal, antiviral, anti-cancer, anti-angiogenic, and anti-inflammatory activities. However, their toxicity is influenced by physicochemical properties such as surface charge, size, and shape. Despite their potential, further research is needed to fully understand their toxicological effects and to develop safer and more effective antimicrobial agents.Metal-based nanoparticles have been extensively studied for biomedical applications, particularly as antimicrobial agents. These nanoparticles are effective against priority pathogens and have non-specific bacterial toxicity mechanisms, making them less prone to resistance development and broadening their antibacterial activity. This review provides a comprehensive overview of the most relevant types of metal nanoparticles used as antimicrobial agents, including gold (AuNPs), silver (AgNPs), copper oxide (CuONPs), and zinc oxide (ZnONPs). The review emphasizes the comparative discussion of their production methods, physicochemical properties, pharmacokinetics, and toxicological risks. The focus is on their potential as alternatives to traditional antibiotics, especially for combating multi-resistant Gram-negative bacteria. The review highlights the mechanisms of action of metal-based nanoparticles, including their ability to interact with bacterial cell surfaces, destabilize cell walls and membranes, induce oxidative stress, and modulate signal transduction pathways. The synthesis methods of metal and metal oxide nanoparticles include chemical reduction, biochemical, electrochemical, wave-assisted, and cementation methods. Each method has its advantages and challenges, with chemical reduction being the most widely used. Silver nanoparticles (AgNPs) are among the most studied metal-based nanoparticles due to their broad antibacterial activity. They are synthesized through various methods, including conventional chemistry, green chemistry, and biological methods. AgNPs are characterized using techniques such as UV-Vis spectrophotometry, X-ray diffractometry (XRD), transmission electron microscopy (TEM), and infrared spectroscopy (IR). Their pharmacokinetics, absorption, distribution, metabolism, and excretion are influenced by factors such as dose, administration route, and species. AgNPs exhibit antimicrobial activity through mechanisms such as adhesion to bacterial surfaces, destabilization of cell walls and membranes, induction of oxidative stress, and modulation of signal transduction pathways. They also show potential in other biomedical applications, including antifungal, antiviral, anti-cancer, anti-angiogenic, and anti-inflammatory activities. However, their toxicity is influenced by physicochemical properties such as surface charge, size, and shape. Despite their potential, further research is needed to fully understand their toxicological effects and to develop safer and more effective antimicrobial agents.