This study investigated the antimicrobial mechanism of simvastatin, a cholesterol-lowering drug that has shown in vitro activity against Staphylococcus aureus. The focus was on the bacterial HMG-CoA reductase, a enzyme player in the mevalonate pathway. The enzyme from S. aureus was cloned, expressed in E. coli, and purified for enzymatic assays. Molecular modeling studies were performed using AlphaFold 3 and molecular docking to explore the interaction between simvastatin and the active site of the bacterial enzyme.