Abstract: Background and Objective: Streptococcus mutans is a major causative pathogen of dental caries, which is a multifactorial oral infection resulting in progressive tooth destruction. Several medicinal plants, including Morus alba (mulberry tree) have been used in folk medicine for the treatment and prevention of dental caries. The objectives of this study were to evaluate the antibacterial and anti-cariogenic activities of the M. alba leaf extracts against S. mutans and to develop a chewing gum containing the extract. Materials and Methods: The MIC and MBC were determined by using broth dilution and drop plate methods, respectively. Biofilm formation and glycolytic pH drop assays were performed to evaluate the anti-cariogenic activity. High-performance liquid chromatography was used for phytochemical analysis of the extracts. The chewing gum containing the M. alba leaf ethanolic extract was prepared by varying different types and concentrations of ingredients. The freeze-thaw cycle testing was conducted to determine the stability of the developed chewing gum. Results: The ethanolic and aqueous M. alba leaf extracts possessed antibacterial activity against S. mutans with the MICs of 0.14 and 5 mg mL–1, respectively. The ethanolic extract at the sub-MICs significantly inhibited both acid production and biofilm formation of S. mutans. The phytochemical analysis showed that the concentrations of chlorogenic acid and rutin in the ethanolic extract were significantly higher than those in the aqueous extract. Two satisfactory chewing gum formulas with good stability, gum A and B, were obtained. The gum B formula was found to have the better performance. Conclusion: The results from this study demonstrated the anti-cariogenic role of M. alba leaves even at the low concentration of sub-MICs. The prepared chewing gum B formula can potentially be further developed as a medicated chewing gum for the prevention of dental caries in the near future.