The free radical scavenging activity of various enzymatic extracts prepared from Hericium erinaceum was evaluated by using an ESR spectrometer. For this study, H. erinaceum was enzymatically hydrolyzed by eight carbohydrases and eight proteases. All of the hydrolyzed extracts scavenged DPPH, hydroxyl, superoxide, and alkyl radicals. Especially, the the pepsin-treated extracts (PTE) exhibited the highest scavenging activity on hydroxyl radical, which is deemed of the strongest radical. Also, the neuroprotective effects of PTE against hydrogen peroxide-induced oxidative stress in PC12 cells were investigated. PTE stimulated the expression of Bcl-2, on the contrary, the extracts suppressed the expression of Bax. These results indicate that PTE possess antioxidative activity on PC12 cells.