Biofilms in the mouth are responsible for the progression of most oral diseases, among which tooth caries is the most prevalent and costly. Owing to the intraoral environment, conventional antibiotics have a limited residence time in oral biofilms, which leads to poor inhibition of dental plaque. To overcome this problem, we drew inspiration from cell membrane-coated nanoparticles (CMCNPs) and synthesized LA/TCS@PLGA-NPs by encapsulating triclosan (TCS)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TCS@PLGA-NPs) with a Lactobacillus acidophilus (LA) outer membrane. The aim of this investigation was to examine how LA/TCS@PLGA-NPs penetrate Streptococcus sanguinis, Streptococcus gordonii and S. mutans (S.s+S.g+S.m ) cariogenic biofilms and inhibit the cariogenic extracellular polymeric substances (EPSs) in these biofilms. The LA/TCS@PLGA-NPs were stable in terms of size, zeta potential, and sustained drug release kinetics. Moreover, the LA/TCS@PLGA-NPs inherited the adhesion ability of the L. acidophilus outer membrane, and compared with the uncoated TCS@PLGA-NPs, the LA/TCS@PLGA-NPs could adhere to and reside in tri-streptococcal species biofilms more extensively and penetrate the inner biofilm layer more deeply with time. Additionally, the LA/TCS@PLGA-NPs disrupted the structure of the tri-streptococcal species biofilms and reduced the levels of the virulence factor EPSs, biomass, total protein and dry weight. Additionally, in vivo, LA/TCS@PLGA-NPs alleviated the degree or even prevented the occurrence of caries. The nanoparticles also exhibited favorable safety in vivo. The results indicate the excellent application potential of LA/TCS@PLGA-NPs in the treatment of oral diseases caused by biofilms.