Aims: The aim of the present study was to investigate the anti-Streptococcus mutans activity and the in vitro effects of subminimal inhibitory concentrations of guaijaverin isolated from Psidium guajava Linn. on cariogenic properties of Strep. mutans. Methods and Results: Bioautography-directed chromatographic fractionation, yield biologically active compound, quercetin-3-O-alpha-L-arabinopyranoside (guaijaverin), from crude methanol extract of P. guajava. Growth-inhibitory activity of the compound against Strep. mutans of both clinical and type strain cultures was evaluated. The anti-Strep. mutans activity of the guaijaverin was found to be bacteriostatic, both heat and acid stable and alkali labile with the minimum inhibitory concentration (MIC) of 4 mg ml(-1) for MTCC 1943 and 2 mg ml(-1) for CLSM 001. The sub-MIC concentrations (0.0078-2 mg ml(-1)) of the guaijaverin were evaluated for its cariogenic properties such as acid production, cell-surface hydrophobicity, sucrose-dependent adherence to glass surface and sucrose-induced aggregation of Strep. mutans. Conclusions: The active flavonoid compound, quercetin-3-O-alpha-L-arabinopyranoside (guaijaverin) demonstrated high potential antiplaque agent by inhibiting the growth of the Strep. mutans. Significance and Impact of the Study: This study demonstrated the new growth-inhibitory compound guaijaverin against Strep. mutans and led to the acceptance of traditional medicine and natural products as an alternative form of health care.