Abstract Nanohybrids, synthesized via silver nitrate reduction in the presence of silicate clay, exhibit a high potency against bacterial growth. The plate-like clay, due to its anionic surface charges and a large surface area, serves as the support for the formation of silver nanoparticles (AgNPs) ∼30 nm in diameter. The nanohybrid consisting of Ag/silicate at a 7/93 weight ratio inhibited the growth of dermal pathogens including Staphylococcus aureus ( S. aureus ), Pseudomonas aeruginosa and Streptococcus pyrogens , as well as the methicillin- and oxacillin-resistant S. aureus (MRSA and ORSA). Scanning electron microscope revealed that these nanohybrids were adherent on the surface of individual bacteria. The thin silicate plates provide a surface for immobilizing AgNPs in one highly concentrated area but prevent them from entering the cell membrane. Subsequent cytotoxicity studies indicated that surface contact with the reduced AgNPs on clay is sufficient to initiate cell death. This toxicity is related to a loss in membrane integrity due to reactive oxygen species (ROS) generation. The hybridization of AgNPs on clay surface is viable for generating a new class of nanohybrids exhibiting mild cytotoxicity but high efficacy for battling drug-resistant bacteria.