Flavonolignans, for example, silymarin and silybin, have interesting biological activities. For the first time, three new flavonolignans named oenanthenoid A-C (1–3) and nine known flavonolignan derivatives (4–12) were isolated from Oenanthe javanica. Comprehensive spectroscopic data analysis and references were used to identify all of the compounds. The anti inflammatory activities of these isolates (1–12) on RAW264.7 macrophage cells were investigated. Three new compounds (1–3) demonstrated anti inflammatory activity with IC50 values ranging from 6.5 ± 0.6 to 14.7 ± 1.6 µM. Furthermore, two compounds (11 and 12) demonstrated moderate anti inflammatory activity, with IC50 values ranging from 24.1 ± 1.2 to 62.5 ± 1.9 µM.