Introduction: Rambutan-honey pharmaceutical grade (RHPG) is one of ingredients that have been used as a topical application for oral wound healing. Rambutan honey have been known contain rutin flavonoid compound, H2O2, glucose, and acid pH which causes its antibacterial activities. Microorganisms commonly found in the oral cavity such as Streptococcus mutans and Staphylococcus aureus can be pathogenic if the wound environment is compro- mised. The aim of this study was to determine antibacterial effect of RHPG to Streptococcus mutans and Staphylo- coccus aureus bacterial growth. Methods: This study used a sample of rambutan-honey pharmaceutical grade divid- ed into 6,25%, 12,5%, 25%, 50%, and 100% concentrations. Each concentration tested with cup diffusion test on S. mutans and S. aureus and incubated for 18-24 hours. Antibacterial effect with minimum inhibitory concentration (MIC). Data were analyzed statistically (ANOVA and Duncan test, P<0.05). Results: RHPG (6,25%, 12,5%, 25%, 50%, and 100% concentrations) has very strong antibacterial effect to S. mutans (p=0.000) with 23.22mm, 27.44mm, 29.89mm, 34.47mm, 37.23mm MIC respectively but has not antibacterial effect to S. aureus in whole concentration. Duncan test showed RHPG 50% concentration have optimum concentration as antibacterial. Conclusion: There was antibacterial effect of RHPG to Streptococcus mutans but did not have antibacterial activity against S. aureus.