Cotinus coggygria Scop. (Anacardiaceae) is traditionally used in Türkiye for wound and burn treatment. A series of nano/micro-sized polymeric particles were prepared from aqueous and ethanol extracts of Cotinus coggygria leaves by reverse micellar microemulsion polymerization. Optimization studies were conducted with the effect of the solvent/surfactant, crosslinker, and extract components and their amount. Thermal Gravimetric Analysis, Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, and Zeta Potential measurement were conducted. In vitro antimicrobial microdilution method was utilized with minor modifications against Staphylococcus aureus ATCC 6538. Polymeric particles' toxicity and in vivo antimicrobial effect were evaluated on the life span Caenorhabditis elegans assay and C. elegans-S. aureus infection model, respectively. Synthesized microparticles (GS04) in vitro antimicrobial activity was investigated against S. aureus ATCC 6538. GS04 (Minimum Inhibitory Concentration = 62.5 μg/mL) microparticle was more effective against S. aureus, demonstrating no nematode survival changes at 500, 250, 125, 62.5, 31.25, and 15.625 μg/mL concentrations, achieving anti-infective effect at 250-15.625 μg/mL for GS04. Nanoparticles did not affect the colonization of S. aureus in the nematode model system. Therefore, concentrations of the selectively nontoxic anti-infective effect of synthesized nanoparticles from C. coggygria were identified for the first time against S. aureus ATCC 6538.