Propionibacterium acnes have been recognized as one of the main agents in pathogenesis of acne. In vitro studies showed that rambutan and mangosteen rind extract containing bioactive compounds had antibacterial and antioxidant activity. Thus, the purpose of this study evaluated anti-acne of ethanol extract of rambutan and mangosteen rind against P. acnes. This research was used methods include extraction rambutan and mangosteen rind by soxhlet technique, antibacterial activity by agar well diffusion, broth dilution, correlation its activity with total flavonoid and α-mangostin contents. The content of total flavonoids was found rambutan rind was 1.25g/100 g crude extract. The percentage of mangostin content in dried powder weight and dried crude extract accounted for 1.5% and 14.26%, respectively. Three strains isolated (PaT1, PaT2 and Pa0B) had similar to Propionibacterium sp. about morphology character and biochemical test. Molecular biology methods were used for the identification of infecting P. acnes strain with the similarity 94% (977/1039) to Propionibacterium acnes PA­_12_1_L1. The Garcinia mangostana extract had the greatest inhibitory effect against P. acnes. The inhibitory effects of P. acnes of mangosteen peel extract with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 8 μg/mL and 31.25 μg/mL, respectively. Particularly, ethanol the rambutan pericarp extract found to be effective against P. acnes (at diameter of the inhibition zone at 19.7 mm) which had strong inhibitory effects at concentration 40,000 µg/mL. The result showed that the MIC, MBC values of extract were at 200 µg/mL and ≥ 200 µg/mL, respectively against P. acnes. Therefore, extract of ethanol rambutan and mangosteen peel had potential to be used as antimicrobial activities and possibility for alternative treatment of acnes.