Abstract: Phytochemical investigation on the ethanol extract of a well-known medicinal herb Leonurus japonicus, led to the separation of 18 labdane type diterpenoids ( 1 − 18 ). Through comprehensive spectroscopic analyses and quantum chemical calculations, these compounds were structurally characterized as six new interesting 5,5,5-di-spirocyclic ones ( 1 − 6 ), two new ( 7 and 8 ) and six known ( 13 − 18 ) interesting 6,5,5-di-spirocyclic ones, a new rare 14,15-dinor derivative ( 9 ), and three new ones incorporating a γ-lactone unit ( 10 − 12 ). An in vitro neuroprotective assay in RSC96 cells revealed that compounds 7 and 12 exhibited neuroprotective activity in a concentration-dependent way, comparable to the reference drug N-acetylcysteine.