Six undescribed sesquiterpene lactones (1-6) and fifteen known compounds (7-21) were isolated from Seriphidium transiliense. The chemical structures were determined by extensive NMR spectroscopic data, HRESIMS, ECD and X-ray diffraction. Among the known compounds, twelve known compounds were isolated for the first time from this plant, including taurine (9), 11-epitaurin (10), alpha-santonin (11), artesin (13), 11-epiartesin (14), 1 alpha hydroxy-3(1-acetoxyeudesm-4-en-6(1, 7 alpha, 11(1H-12, 6-olide (15), 1 alpha-hydroxy-3(1-acetoxyeudesm-4-en-6(1, 7 alpha, 11 alpha H-12, 6-olide (16), artegallin (17), 8 alpha-hydroxytaurin (18), 8 alpha-acetoxytaurine (19), methyl-4 alpha-hydroxy-11 (13)-eudesmen-12-oatesaniculamoid D (20), and saniculamoid D (21). The absolute configuration of 2 was determined by X-ray. The X-ray crystal structures of 15 and 16 were reported for the first time. At a concentration of 20 mu M, all compounds (1-21) showed significant inhibition of NO production in LPS- stimulated BV2 cells. Among them, compounds 3 and 4 inhibited NO release with IC50 values of 19.30 and 22.05 mu M, respectively. Based on the present results, these compounds may be potential anti-inflammatory agents.