The synthesis of water-insoluble glucans by S. mutans is one of the most important contributors to the maturation of dental plaque. In the present study, several herbal medicines, including Notoginseng Radix, Perillae Rhizoma, and Psoraleae Semen, at least partially inhibited the synthesis of water-insoluble glucans, although Notoginseng Radix and Perillae Rhizoma did not inhibit the growth of oral bacteria. These results suggest that Notoginseng Radix and Perillae Rhizoma may reduce the synthesis of water-insoluble glucans by inhibiting the enzymatic activity of the S. mutans GTase rather than by inhibiting bacterial growth. Furthermore, this is the first report that Notoginseng Radix or Perillae Rhizoma suppresses the synthesis of water-insoluble glucans.