Combination of chlorhexidine (CHX) and silver ions could engender synergistic bactericidal effect and improve the bactericidal efficacy. It is highly desired to develop an efficient carrier for the antiseptics codelivery targeting infection foci with acidic microenvironment. In this work, monodisperse mesoporous silica nanoparticle (MSN) nanospheres were successfully developed as an ideal carrier for CHX and nanosilver codelivery through a facile and environmentally friendly method. The CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) exhibited a pH-responsive release manner of CHX and silver ions simultaneously, leading to synergistically antibacterial effect against both gram-positive
Staphylococcus aureus
and gram-negative
Escherichia coli
. Moreover, the effective antibacterial concentration of Ag-MSNs@CHX showed less cytotoxicity on normal cells. Given their synergistically bactericidal ability and good biocompatibility, these nanoantiseptics might have effective and broad clinical applications for bacterial infections.