In this study, the chemical composition and anti-inflammatory activities of hydrodistilled essential oil from Farfugium japonicum were investigated for the first time. The chemical constituents of the essential oil were further analyzed by GC-MS and included 1-undecene (22.43%), 1-nonene (19.83%), β-caryophyllene (12.26%), α-copaene (3.70%), γ-curcumene (2.86%), germacrene D (2.69%), and 1-decene (2.08%). The effects of the essential oil on nitric oxide (NO) and prostaglandin E2 (PGE₂) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. The results indicate that the F. japonicum essential oil is an effective inhibitor of LPS-induced NO and PGE₂ production in RAW 264.7 cells. These inhibitory effects of the F. japonicum essential oil were accompanied by dose-dependent decreases in the iNOS and COX-2 mRNA expression. In order to determine whether F. japonicum essential oil can safely be applied to human skin, the cytotoxic effects of F. japonicum essential oil were determined by colorimetric MTT assays in human dermal fibroblast and keratinocyte HaCaT cells. F. japonicum essential oil exhibited low cytotoxicity at 100 μg/mL. Based on these results, we suggest that F. japonicum essential oil may be considered a potential anti-inflammatory candidate for topical application.