Objective: To investigate the antimicrobial activity (in vitro) of polysaccharide gel (PG) extracted from fruit-hulls of durian (Durio zibethinus) against Streptococcus mutans. Method: Inhibitory activity of PG against S. mutans was determined by microbiological assay using broth dilution method and time killing method. S. mutans was grown in Tryptic soy broth (TSB) with different concentrations of PG (1, 5, 10, 15, 20 and 35mg/ml) at 37°C for 24 hours. Its survival was evaluated in comparison to the control using drop plate method. Results: The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of PG in TSB medium against S. mutans were 20 and 35mg/ml, respectively. At the concentration of 35mg/ml PG in TSB medium, the bacterial survival was declined to zero in 4-hour incubation. Conclusion: PG, at 20 and 35mg/ml, produced inhibitory and bactericidal activities against S. mutans, respectively. This study was supported by Research and Development Fund, Faculty of Dentistry, Chulalongkorn University.