Using nanomaterials is a novel strategy to eliminate drug resistance against bacteria. Nanoparticles with metal sites show antimicrobial activities that counteract or obstruct antibiotic-resistant mechanisms expressed by the pathogens. Here, a nanocomposite based on mesoporous silica nanoparticles with active sites of silver, and a combination of imipenem and meropenem as antibiotic drugs, was synthesized and characterized using different physicochemical methods. The antibacterial assessments exhibited sensitivity by Staphylococcus aureus (S. aureus), Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) toward the synthesized composite, which showed a suitable safety profile in human cells. This composite has an excellent synergic mechanism based on reactive oxygen species (ROS) to kill bacteria due to penetrating the microbial membrane. In addition, this composite is resistant to hydrolysis by plasmids and chromosomally mediated β-lactamases. This nanocomposite showed extraordinary antiseptic power against Gram-positive and Gram-negative microbes.