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Antimicrobial resistance (AMR) is a significant concern to society as it threatens the effectiveness of antibiotics and leads to increased morbidity and mortality rates. Innovative approaches are urgently required to address this challenge. Among promising solutions, two dimensional (2-D) nanomaterials with layered crystal structures have emerged as potent antimicrobial agents owing to their unique physicochemical properties. This antimicrobial activity is largely attributed to their high surface area, which allows for efficient interaction with microbial cell membranes, leading to physical disruption or oxidative stress through the generation of reactive oxygen species (ROS). The latter mechanism is particularly noteworthy as it involves the degradation of these nanomaterials under specific conditions, releasing ROS that can effectively kill bacteria and other pathogens without harming human cells. This study explores the antimicrobial properties of a novel biodegradable nanomaterial based on 2-D transition metal trichalcogenides, FePS 3 , as a potential solution to drug-resistant microbes. Our findings indicate that FePS 3 is an exceptionally effective antimicrobial agent with over 99.9% elimination of various bacterial strains. Crucially, it exhibits no cytotoxic effects on mammalian cells, underscoring the potential for safe biomedical application. The primary mechanism driving the antimicrobial efficacy of FePS 3 is the release of ROS during biodegradation. ROS has a crucial role in neutralizing bacterial cells, conferring significant antipathogenic properties to this compound. The unique combination of high antimicrobial activity, biocompatibility, and biodegradability makes FePS 3 a promising candidate for developing new antimicrobial strategies. This research contributes to the increasing body of evidence supporting the use of 2-D nanomaterials in addressing the global challenge of AMR, offering a potential pathway for the development of advanced, effective, and safe antimicrobial agents.