Although numerous studies have focused on the antioxidant, antimicrobial and immunomodulatory effectof RJ or RJPs, only a few studies have reported on the neuroprotective effects of RJPs. In this regard, this studymainly investigates the neuroprotective effect of RJPs digested from royal jelly proteins on nerve cells. First,water-soluble RJPs were digested by bee larva entero-enzymes (intestinal canal enzyme solution). Then, crudeRJPs were fractioned into various components using high-performance liquid chromatography (RP-HPLC)methods. Furthermore, purified RJPs were investigated in N2a/APP695 cells to explore their effects on the metabolismof Aβ and the possible mechanism. This work provides new evidence that RJPs obtained from royal jellyhave neuroprotective functions in some nerve cells and could be serve as novel natural BACE1 inhibitors, whichmay provide beneficial effects for AD patients.