Periodontitis is a severe form of gum disease caused by bacterial plaque that affects millions of people and has substantial worldwide health and economic implications. However, current clinical antiseptic and antimicrobial drug therapies are insufficient because they frequently have numerous side effects and contribute to widespread bacterial resistance. Recently, nanotechnology has shown promise in the synthesis of novel periodontal therapeutic materials. Nanoparticles are quickly replacing antibiotics in the treatment of bacterial infections, and their potential application in dentistry is immense. The alarming increases in antimicrobial resistance further emphasize the importance of exploring and utilizing nanotechnology in the fight against tooth diseases particularly periodontitis. We developed 16 different combinations of mesoporous silica nanomaterials in this study by ageing, drying, and calcining them with 11 different metals including silver, zinc, copper, gold, palladium, ruthenium, platinum, nickel, cerium, aluminium, and zirconium. The antibacterial properties of metal-doped silica were evaluated using four distinct susceptibility tests. The agar well diffusion antibacterial activity test, which measured the susceptibility of the microbes being tested, as well as the antibacterial efficacy of mesoporous silica with different silica/metal ratios, were among these studies. The growth kinetics experiment was used to investigate the efficacy of various metal-doped silica nanoparticles on microbial growth. To detect growth inhibitory effects, the colony-forming unit assay was used. Finally, MIC and MBC tests were performed to observe the inhibition of microbial biofilm formation. Our findings show that silver- and zinc-doped silica nanoparticles synthesized using the sol-gel method can be effective antimicrobial agents against periodontitis-causing microbes. This study represents the pioneering work reporting the antimicrobial properties of metal-loaded TUD-1 mesoporous silica, which could be useful in the fight against other infectious diseases too.