ObjectiveThis study aims to evaluate the antimicrobial activity of decapeptide, a novel antimicrobial peptide, against several major cariogenic and periodontopathogenic bacteriain vitro.MethodsIn this study, we investigated the antimicrobial activity of decapeptide againstStreptococcus mutans(S. mutans),Streptococcus sobrinus,Lactobacillus acidophilus,Streptococcus sanguis,Streptococcus gordonii,Actinomyces viscosus,Actinomyces naeslundii,Porphyromonas gingivalis,Prevotella intermedia,Fusobacterium nucleatum,Actinobacillus actinomycetemcomitans, andSaccharomyces albicans in vitrousing the agar diffusion method and broth dilution method. Furthermore, a time–kill kinetic study of decapeptide againstS. mutanswas performed.ResultsThe results showed that decapeptide exhibited antimicrobial activity against various oral bacteria and fungi. The minimum inhibitory concentration (MIC) of main cariogenic bacteria ranged from 62.5 μg·mL-1to 125 μg·mL-1, and the MIC of periodontopathogenic bacteria tested ranged from 250 μg·mL-1to 1 000 μg·mL-1. Among the bacteria tested, decapeptide had a strong inhibitory effect on cariogenicS. mutans. Results of the time–kill kinetic studies showed that decapeptide reduced the viable counts ofS. mutansby more than one order of magnitude after 20 min of incubation, and thoroughly killedS. mutansafter 30 min. No viable cells could be detected after 24 h of incubation.ConclusionThis study suggest that decapeptide might have potential clinical application in treating dental caries by killingS. mutanswithin dental plaque.