This study presents an optimized microwave-assisted method for the green synthesis of silver nanoparticles (AgNPs) using a root extract obtained from Pelargonium sidoides DC. The influence of temperature, reagent concentration, and irradiation time was systematically investigated to enhance synthesis yield. Characterization techniques including XRD, UV-vis, FTIR, XPS, and zetametry were employed to confirm the successful formation of nanoparticles with a metallic silver core (∼17 nm) functionalized with organic molecules derived from the plant extract. The cytotoxicity of AgNPs was assessed using a cell viability assay, while the Minimum Inhibitory Concentration (MIC) of nanoformulation against pathogenic bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and the carbapenem-resistant Klebsiella pneumoniae (KPC), was determined using the Broth microdilution method. The nanoformulation synthesized with P. sidoides extract exhibited a dose-dependent response, demonstrating superior antimicrobial efficacy compared to the pure plant extract in most cases. The MIC values ranged from 0.85 to 17.1 μg mL-1, with particularly strong performance against the drug resistant KPC strain. The enhanced antimicrobial effect is attributed to the synergistic action of the metallic silver core and phytochemicals from P. sidoides on the surface of nanoparticles, which also contribute to notable colloidal stability of AgNPs at physiological pH levels.