Silver nanoparticles (AgNPs) have become known as a broad‐spectrum antimicrobial agent. The antimicrobial activity of AgNPs is dependent on the particle size and the dispersion status. In this study, a simple and effective approach is developed for sequestering the biosynthesized AgNPs in silica composites during the gel formation of MCM‐41. Composites with different Ag concentrations of 0.034% (Ag1@MCM‐41), 0.151% (Ag2@MCM‐41), and 0.369% (Ag3@MCM‐41) are synthesized and then heated at 400 °C to produce Ag1@MCM‐41H, Ag2@MCM‐41H, and Ag3@MCM‐41H, respectively. The samples are characterized by flame atomic absorption spectrometry, Fourier‐transform infrared spectroscopy, X‐ray diffraction, N2 physisorption, scanning electron microscopy, transmission electron microscopy, and thermogravimetric analysis. The AgNPs are confirmed to be highly dispersed in the amorphous silica framework. The antimicrobial activity of the AgNP–silica samples is investigated against Staphylococcus aureus, Escherichia coli, and Candida albicans using the cup–plate and the plate‐count techniques. The results show an excellent antimicrobial effect of these samples against the studied microorganisms. Importantly, the AgNP–silica samples are found to be stable up to 58 months under ambient conditions. These stable and powerful antimicrobial composites provide a more practical and effective strategy for combating biomedical pathogens and public health threats.