The emergence of multidrug-resistant organisms poses a significant challenge to public health worldwide. In response, plant-based nanoparticles have garnered attention for their potential as novel antimicrobial agents. These nanoparticles are derived from various plant sources and exhibit inherent antimicrobial properties due to their phytochemical composition. Nanoparticles synthesized from spinach (Spinacia oleracea) and orange (Citrus sinensis) extracts, loaded with salts of Cu and Zn, were evaluated for their antimicrobial activity against multidrug-resistant bacteria. Antimicrobial efficacy was assessed through agar well diffusion assays against clinically relevant multidrug-resistant bacterial strains of Pseudomonas aeruginosa MTCC 74, Staphylococcus aureus MTCC 902, Klebsiella pneumoniae MTCC 661. The nanoparticles exhibited potent antimicrobial effects, significantly inhibiting the growth of tested bacteria even when compared to commercially available antibiotics. These findings highlight the potential of plant-based nanoparticles loaded with Cu and Zn salts as effective agents against multidrug-resistant bacteria, offering a promising avenue for future antimicrobial therapies.