Biotransformation is often used to improve chemical activity. We evaluated the antimicrobial activity of rhapontigeuin, converted from rhapontin after treatment with Pectinex. Rhapontigenin showed 4-16 times higher antimicrobial activity than rhapontin. The activity was higher against Gram-positive strains than Gram-negative strains. Minimum inhibitory concentrations (MICs) of rhapontigenin, retinol, and five antibiotics were determined by the microbroth dilution method for antibiotic-sensitive and -resistant Propionibacterium acnes. We also investigated the in vitro antibacterial activity of rhapontigenin in combination with antibiotic against antibiotic-resistant P. acnes. The antibiotic combination effect against resistant P. acnes was studied by the checkerboard method. The combination formulations (rhapontigenin and clindamycin, retinol and clindamycin) showed synergistic effects on the inhibition of the growth of clindamycin-resistant P. acnes. It is predictable that the combination of antibiotics with rhapontigenin is helpful to treat acne caused by antibiotic-resistant P. acnes. The antibacterial activity of rhapontigenin was enhanced by biotransformation.