Streptococcus mutans is a cariogenic pathogen in humans. To persist in the oral cavity, S. mutans is resistant against several antibacterial factors derived from the host. In this study, we investigated the mechanism of resistance to cationic antimicrobial peptides (AMPs), which are innate immune factors in humans. Because dltA-D (teichoic acid biosynthesis) was reported to affect the susceptibility to AMPs in other bacterial species, we evaluated the susceptibility of a dltC knockout mutant of S. mutans to the AMPs human beta-defensin-1 (hBD1), hBD2, hBD3 and LL37. The dltC mutant exhibited significantly increased susceptibility to AMPs. Regulation of dltC expression involved CiaRH, a two-component system. Expression of dltC in the wild-type strain was significantly increased in biofilm cells compared with that in planktonic cells, whereas expression was not increased in a ciaRH knockout mutant. In biofilm cells, we found that susceptibility to LL37 was increased in the ciaRH mutant compared with that in the wild type. From these results, it is concluded that Dlt is involved in the susceptibility of S. mutans to AMPs and is regulated by CiaRH in biofilm cells.