Antimicrobial peptides play an important role in the human innate immune defense system. In the oral cavity, a number of antimicrobial peptides, including defensins and LL37, are produced from various tissues such as salivary glands, gingival epithelium, tongue and buccal mucosa. These peptides are believed to function as a host defense system by controlling the activities of commensal bacteria and thus preventing the colonization and growth of pathogenic bacteria in oral cavity. Two major oral diseases, dental caries and periodontitis are known as infectious diseases. Therefore, it is of great interest to elucidate the mechanisms underlying the onset and progression of these diseases by investigating the interaction between cariogenic, or periodontopathogenic bacteria and antimicrobial peptides. Since these peptides have a broad antimicrobial spectrum, they are implicated as possible therapeutic agents. Therefore, in this review, we first focus on the susceptibility of oral bacteria, especially cariogenic and periodontopathogenic bacteria, to antimicrobial peptides, and then we discuss their potential diagnostic and clinical therapeutic uses.