Seventy-five compounds, including 21 new compounds (1-21), were isolated from the root bark of Cudrania tricuspidata. The structures of the isolated compounds were elucidated by interpretation of their spectroscopic data. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced cell death, and nine compounds had activities with EC50 values of 1.9-30.2 μM. The 75 isolated compounds along with 34 previously reported xanthones were tested also for neuroprotective effects against the 1-methyl-4-phenylpyridinium ion (MPP(+)) and oxygen glucose deprivation (OGD)-induced cell death. Three compounds were active against MPP(+)-induced cell death with EC50 values of 0.2-10.3 μM, and 23 compounds were active in the OGD model with EC50 values of 2.9-35.5 μM.