These days the emergence of multidrug-resistant (MDR) gram-negative bacteria poses a significant threat to public health globally. Traditional antibiotics are becoming ineffective due to antibiotic resistance. Bacteria uses efflux pumps, enzymatic degradation, and biofilm formation to become resistant. Medicinal plant-derived nanoparticles (MPNPs) have gained attention as a novel alternative for combating bacterial infections due to their biocompatibility, eco-friendly synthesis, and antibacterial properties. These nanoparticles exhibit multiple mechanisms of action, including disrupting bacterial membranes, generating reactive oxygen species (ROS), and inhibiting biofilm formation. In this chapter, we’re going to talk about how these nanoparticles are made, what kinds of plants they come from, how they actually work against bacteria, and where they might be used in the real world—whether in medicine or other industries. There are definitely still hurdles to overcome, but blending old-school plant knowledge with modern nanotech could end up giving us some powerful tools to deal with resistant infections in the near future. The challenges and future prospects of MPNPs in combating MDR bacterial infections are discussed. By integrating nanotechnology with traditional plant-based medicine, MPNPs hold great promise for developing next-generation antimicrobial therapies.