Dental caries is the most common disease in the human mouth. is the primary cariogenic bacterium. Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria. The polyphenol-rich extract from propolis inhibits growth and biofilm formation, as well as the genes involved in virulence and adherence, through the inhibition of glucosyltransferases (GTF). However, because the chemical composition of propolis is highly variable and complex, the mechanism of its antimicrobial action and the active compound are controversial and not completely understood. Caffeic acid phenethyl ester (CAPE) is abundant in the polyphenolic compounds from propolis, and it has many pharmacological effects. In this study, we investigated the antibacterial effects of CAPE on common oral cariogenic bacteria ( , , , and ) and its effects on the biofilm-forming and cariogenic abilities of CAPE shows remarkable antimicrobial activity against cariogenic bacteria. Moreover, CAPE also inhibits the formation of biofilms and their metabolic activity in mature biofilms. Furthermore, CAPE can inhibit the key virulence factors of associated with cariogenicity, including acid production, acid tolerance, and the bacterium's ability to produce extracellular polysaccharides (EPS), without affecting bacterial viability at subinhibitory levels. In conclusion, CAPE appears to be a new agent with anticariogenic potential, not only via inhibition of the growth of cariogenic bacteria.