Dental caries is a worldwide public healthcare concern, and is closely related to the acidic environment that caused by bacterial decomposition of food. In this study, a two-step ion exchange liquid-phase stripping method was applied to strip out vermiculite (VMT) nanosheets, then amorphous calcium phosphate (ACP) and dextran were inserted between the VMT nanosheets interlayer to obtain a composite two-dimension nanosheets (VMT/ACP/Dextran). VMT/ACP/Dextran composite nanosheets exhibited excellent biocompatibility and could provide exogenous Ca²⁺and PO₄^3- from ACP, provide SiO₄^4-, Mg²⁺, Fe²⁺ and obtain buffering pH and antibacterial properties from VMT, as well as improve suspension stability and targeting Streptococcus mutans through glucan. The in vitro study showed that the composite materials could promote the mineralization and sealing of dentin tubules by releasing active ions, buffer pH 4.5 (a value close to the pH in the dental plaque environment) to pH 6.6-7.1 (values close to the pH in human saliva) through ion exchange, and exert antibacterial effects by targeting Streptococcus mutans and exerting oxidase like and peroxidase like activities to produce reactive oxygen species (ROS). The in vivo animal study showed that daily cleaning teeth using VMT/ACP/Dextran composite nanosheets could effectively reduce the incidence rate and severity of dental caries in rats. Taking together, the developed VMT/ACP/Dextran composite nanosheets, which integrated the excellent properties of VMT, ACP and dextran, can effectively prevent dental caries through a combination of factors such as buffering acids, antibacterial properties, and promoting calcification, and may be used as an active ingredient for daily oral hygiene or filling materials to prevent and treat dental caries.