Abstract: Five undescribed sesquiterpenoids ( 1 – 5 ), and nine known sesquiterpenoids ( 6 – 14 ) were obtained from the fruits of Litsea lancilimba Merr. by LC-MS/MS molecular networking strategies. Litsemene A ( 1 ) possessed a unique 8-member ring through unexpected cyclization of the methyl group on C-10 of guaiane. Their structures were elucidated by spectroscopic techniques including IR, UV, NMR, HR-ESI-MS, and their absolute configurations were assigned by ECD calculations. All isolated sesquiterpenoids were analyzed by bioinformatics and evaluated for their neuroprotective effects against H₂O₂-induced injury in human neuroblastoma SH-SY5Y cells.