Neuroprotective reagents to protect the nerve cells against oxidative stress and other damages are potentially effective for the medical treatment of Parkinson’s disease. Petasites japonicus, a wild vegetable, belongs to the family Compositae and its extract has shown the neuroprotective effects. A further phytochemical investigation of P. japonicus for neuroprotective substances led to the isolation of eight new (1–8) and two known (9 and 10) sesquiterpenes. Their structures were elucidated on the basis of extensive 1D and 2D NMR (HMQC, HMBC, 1 H– 1 H COSY, and NOESY) spectroscopic data analyses, and the structure of 1 was confirmed by X-ray crystallography. The neuroprotective activities of these sesquiterpenes were evaluated against cobalt chloride (CoCl 2 )-induced neuronal cell death in human dopaminergic SH-SY5Y cells. Five compounds showed a neuroprotective activity.