Streptococcus mutans is the primary etiological agent of human dental caries. The well-known extraordinary ability of S. mutans to adapt and survive the environment of human mouth is highly acidogenicity and strong exopolysaccharide (EPS) production, a skeleton of dental plaque (biofilm). In this research, the total biofilm biomass, as well as the contents of protein, intracellular polysaccharide (IPS), alkaline soluble polysaccharide (ASP), water soluble polysaccharide (WSP) in the biofilm treated with 150 M α-mangostin was reduced ca. 40% compared to those of the control in ethanol as the vehicle. Two important glycosyltranferases B and C, responsible for biofilm formation by S. mutans, showed to be very sensitive to α-mangostin. Under the treatment condition, biofilm structure was clearly changed. Non-uniform and bigger microcolonies were found in the treated biofilms. Effects of α-mangostin on expression of the virulent genes and the detailed changes in biofilm structure are now under examination. The results showed that the -mangostin is a new and potential anti-biofilm agent of S. mutans UA159.