In this study, we investigated the antibacterial properties of nanostructured Ag@SiO₂–penicillin synthesized from triangular silver nanoplates (Ag NPs) against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteria. The Ag@SiO₂–penicillin nanoparticles contained approximately 33.2 wt% Ag as determined by ICP-OES. Grafting of about 2.8 wt% penicillin on Ag@SiO₂ remarkably enhanced the bactericidal properties against MSSA and MRSA bacteria and showed no cell-death inducing effects towards the A431 cell line.