Antimicrobial resistance (AMR) is a pressing global issue, driving the search for innovative antimicrobial therapies. Antimicrobial photodynamic inactivation (aPDI) presents a promising solution by utilizing molecular oxygen, light, and a photosensitizer to inactivate microorganisms. However, the effectiveness of aPDI can be limited by several factors such as solubility, stability, and efflux pump-mediated resistance. Plasmonic nanoparticles, particularly gold and silver, have emerged as a promising alternative to enhance aPDI. These nanoparticles are distinguished by their unique physical and optical properties, such as high surface area-to-volume ratios and localized surface plasmon resonance. When combined with a photosensitizer, plasmonic nanoparticles can significantly boost the generation of reactive oxygen species (ROS), which are crucial for microbial inactivation. The effectiveness of this approach depends on the careful selection of suitable photosensitizers that complement the nanoparticles. Design considerations for nanoparticles include metal type, shape, and capping agents, all of which impact their performance in aPDI. This chapter reviews recent advancements in leveraging plasmonic nanoparticles to improve aPDI, detailing the mechanisms through which they enhance ROS generation and discussing the associated challenges. It also addresses the responsible development and application of plasmonic nanoparticles, emphasizing the need for a balanced approach to maximize therapeutic benefits while mitigating potential health and environmental risks.