Dental caries is one of the most common chronic diseases worldwide.Streptococcus mutansandCandida albicansare two major pathogens associated with dental caries. Several recent studies revealed thatLactobacillus plantaruminhibitsS. mutansandC. albicansin biofilms and in a rodent model of dental caries. The aim of this study was to investigate the dose-dependent effect ofL. plantarumagainstS. mutansandC. albicansin a planktonic model that simulated a high-caries-risk clinical condition. Mono-, dual-, and multi-species models were utilized, with five doses ofL. plantarum(ranging from 1.0 × 104to 1.0 × 108CFU/mL). Real-time PCR was used to assess the expression of the virulence genes ofC. albicansandS. mutansand the genes ofL. plantarum. Student’st-tests and one-way ANOVA, followed by post hoc tests, were employed to compare the cell viability and gene expression among groups. A dose-dependent inhibition onC. albicansandS. mutanswas observed with increased dosages ofL. plantarum.L. plantarumat 108CFU/mL demonstrated the highest antibacterial and antifungal inhibitory effect in the dual- and multi-species models. Specifically, at 20 h, the growth ofC. albicansandS. mutanswas suppressed by 1.5 and 5 logs, respectively (p< 0.05). The antifungal and antibacterial effects were attenuated in lower doses ofL. plantarum(104–107CFU/mL). The expression ofC. albicans HWP1andECE 1genes andS. mutans lacCandlacGgenes were significantly downregulated with an added 108CFU/mL ofL. plantarum(p< 0.05). The addition of 108CFU/mLL. plantarumfurther inhibited the hyphae or pseudohyphae formation ofC. albicans. In summary,L. plantarumdemonstrated dose-dependent antifungal and antibacterial effects againstC. albicansandS. mutans.L. plantarumemerged as a promising candidate for the creation of novel antimicrobial probiotic products targeting dental caries prevention. Further research is warranted to identify the functional metabolites produced byL. plantarumat different dosages when interacting withC. albicansandS. mutans.