A sesquiterpenoid with an unprecedented 5/5/4 tricyclic skeleton (1), a nor-sesquiterpenoid with a rare 6/7 bicyclic skeleton (2), 10 new sesquiterpenoids (3–12), and six known analogues (13–18) were isolated from the whole plants of Seriphidium transiliense. The structures of compounds 1–12were elucidated by spectroscopic data analysis. Compound 7showed melanogenic promotion activity in murine melanoma (B16) cells more potent than the positive control used, 8-methoxypsoralen (8-MOP). Further mechanistic studies indicated that compound 7promotes melanogenesis through activating the transcription of microphthalmia-associated transcription factor (MITF) and tyrosinase family genes in B16 cells. Moreover, compound 7also inhibited the expression of IFN-γ-chemokine through the JAK/STAT signaling pathway in immortalized human keratinocyte (HaCaT) cells. These results suggest that the sesquiterpenoid 7shows potential activity for treating vitiligo.