Acne, also known as acne vulgaris, is a common disorder of human skin involving the sebaceous gland and Propionibacterium acnes (P. acnes). Although there are a number of treatments suggested for acne, many of them have limitations in their safety and have efficacy issues. Therefore, there is a high demand to develop safe and effective novel acne treatments. In the present study, we demonstrate the protective effects of Rosa davurica Pall. leaves (RDL) extract against P. acnes-induced inflammatory responses in vitro and in vivo. The results showed that RDL dose-dependently inhibited the growth of skin bacteria, including P. acnes (KCTC3314) and aerobic Staphylococcus aureus (KCTC1621) or Staphylococcus epidermidis (KCTC1917). The downregulation of proinflammatory cytokines by RDL appears to be mediated by blocking the phosphorylations of mitogen-activated protein kinase (MAPK) and subsequent nuclear factor-kappa B (NF-κB) pathways in P. acnes-stimulated HaCaT cells. In a mouse model of acne vulgaris, histopathological changes were examined in the P. acnes-induced mouse ear edema. The concomitant intradermal injection of RDL resulted in the reduction of ear swelling in mice along with microabscess but exerted no cytotoxic effects for skin cells. Instrumental analysis demonstrated there were seven major components in the RDL extract, and they seemed to have important roles in the anti-inflammatory and antimicrobial effects of RDL. Conclusively, our present work showed for the first time that RDL has anti-inflammatory and antimicrobial effects against P. acnes, suggesting RDL as a promising novel strategy for the treatment of acne, including natural additives in anti-acne cosmetics or pharmaceutical products.