The strong bactericidal properties of lauric acid (C12:0), a middle chain-free fatty acid commonly found in natural products, have been shown in a number of studies. However, it has not been demonstrated whether lauric acid can be used for acne treatment as a natural antibiotic against Propionibacterium acnes (P. acnes), which promotes follicular inflammation (inflammatory acne). This study evaluated the antimicrobial property of lauric acid against P. acnes both in vitro and in vivo. Incubation of the skin bacteria P. acnes, Staphylococcus aureus (S. aureus), and Staphylococcus epidermidis (S. epidermidis) with lauric acid yielded minimal inhibitory concentration (MIC) values against the bacterial growth over 15 times lower than those of benzoyl peroxide (BPO). The lower MIC values of lauric acid indicate stronger antimicrobial properties than that of BPO. The detected values of half maximal effective concentration (EC(50)) of lauric acid on P. acnes, S. aureus, and S. epidermidis growth indicate that P. acnes is the most sensitive to lauric acid among these bacteria. In addition, lauric acid did not induce cytotoxicity to human sebocytes. Notably, both intradermal injection and epicutaneous application of lauric acid effectively decreased the number of P. acnes colonized with mouse ears, thereby relieving P. acnes-induced ear swelling and granulomatous inflammation. The obtained data highlight the potential of using lauric acid as an alternative treatment for antibiotic therapy of acne vulgaris.