Ultrasmall silver nanoclusters (Ag NCs) are one of the emerging and highly efficient antibacterial agents, owing to the unique features of sub-2 nm particle size and the high abundance of the active Ag+ species. However, practical applications of Ag NCs in biological environment are often hampered by silver oxidization, which results in particle aggregation and loss of antibacterial activity. In this study, for the first time, we develop a facile method to synthesize highly dispersed Ag NCs decorated mesoporous silica nanoparticles (Ag NC-MSNs) capable of long-term and efficient release of Ag+ ions. This novel Ag NC-MSNs nanocomposite was demonstrated as an effective antibacterial agent against both Gram-positive and Gram-negative pathogenic bacteria. Compared with the counterparts Ag NCs and silver nanoparticles decorated mesoporous silica nanoparticles (Ag NP-MSNs), Ag NC-MSNs exhibit 17-fold and 27-fold enhancement in antibacterial potency, respectively. The homogeneous distribution of ultrasmall Ag NCs in the mesoporous architecture of supporting MSNs matrix is crucial for the controlled release of Ag+ ions, leading to the superior broad-spectrum antimicrobial activity. Moreover, the cytotoxicity assay indicated that the effective antibacterial concentration of Ag NC-MSNs shows minimum toxicity on mammalian cells. This new Ag nanocomposite developed in this work is promising for practical applications against various microbial infections. (C) 2019 Elsevier Inc. All rights reserved.