Quassinoids are a class of highly oxygenated degraded triterpenoids exclusively discovered from plants of the Simaroubaceae family. In this study, eight new (1-8) and 15 known quassinoids (9-23) were isolated from an extract of the stems of Picrasma quassioides. The structures were elucidated by spectroscopic analysis and electronic circular dichroism spectra combined with quantum chemical calculations. Compounds 4 and 5 represent the first examples of 18-nor-quassinoids from P. quassioides. All isolates were screened for their neuroprotective activities toward H2O2-induced cell damage in SH-SY5Y cells. Further study revealed that the potential protective activities of these compounds appeared to occur via the suppression of cell apoptosis and downregulation of caspase-3 activation.