Abstract: The purpose of this study is to evaluate the inhibitory effects of crude extract of endophytic Streptomyces sp. ST8 against Streptococcus mutans that is one of the major causes of dental caries and oral diseases. The extract from culture filtrate of endophytic Streptomyces sp. ST8 by ethyl acetate has activity against S. mutans ATCC25175 and 104B. The extract at such concentrations (0.05-5 mg mL-1) showed the inhibition of bacterial adherence on glass surfaces and saliva-coated hydroxyapatite. The crude extract also decreased the activity of glucosyltransferase and glucan-binding lectin from both strains. The very considerable increase in cellular permeability was observed from both strains. These results suggest that the crude extract of endophytic Streptomyces sp. ST8 may be a new potential source for pharmaceutical products used for prevention and/or treatment of dental caries and periodontal disease.