In the present study, we investigated the neuroprotective effects of a purified Corydalis yanhusuo polysaccharide (CYP) on Aβ (25–35)-induced neurotoxicity and explored its underlying molecular mechanisms in PC12 cells. The results showed pretreatment with CYP (25, 50, and 100 μg/ml) prior to Aβ (25–35) exposure significantly protected PC12 cells from Aβ (25–35)-induced cell death, lactate dehydrogenase (LDH) release, DNA fragmentation, mitochondrial dysfunction and mitochondrial cytochrome c release. Moreover, Aβ (25–35)-induced increase of ratio between Bax and Bcl-2 protein expression was dramatically reversed by CYP pretreatment. Furthermore, the addition of CYP led to a significant repressing effect on the elevated protein expression of cleaved caspase-8, caspase-9, and caspase-3 in Aβ (25–35)-treated PC12 cells. Taken together, these findings indicated that protective effect of CYP against Aβ (25–35)-induced toxicity in PC12 cells was probably mediated by inhibition of apoptosis via both mitochondrial apoptotic pathway and death receptor pathway.