Abstract: Four different lanternfish (Benthosema pterotum) protein hydrolysates (LPHs) were obtained by treating the fresh whole fish with Protease A, Protease N, Prozyme 6 or Protamex. The Protease-N treated LPHs showed strong antioxidant activities in the assays of DPPH radical scavenging, Fe2 + chelation, reducing power and SOD-like activity. The sequences of two short oligopeptides with highest antioxidant activity were identified to be Phe-Tyr-Tyr and Asp-Trp. Through an in vitro pepsin–pancreatin simulated gastrointestinal (GI) digestion, we found that both the content and chelating activity of LPHs in the range of ≦ 700 Da increased, indicating that the Protease N-treated LPHs can resist the GI digestion and retain the antioxidant activity. In a H2O2 toxicity test, LPHs were shown able to prevent H2O2-induced DNA damage, whereby the survival rate of neuroblastoma cells (SHSY5Y) significantly increased and the neural synapse outgrowth improved in a dose-dependent manner. LPHs are thus concluded to be high value-added antioxidants and possessed the potential benefit to prevent neurodegenerative disorders from oxidation-induced damage.