Cerebroprotein Hydrolysate (CH) is a nutrient extracted from porcine brain tissue that is rich in bioactive peptides. This study first demonstrated that CH exhibits significant learning and memory enhancement activity through behavioral experiments in APP/PS1 mice. However, the specific components and mechanisms of action remained unclear. Integrated peptidomics and bioinformatics screening identified the peptide KAPGLLPR as a highly promising candidate for cognitive enhancement. KAPGLLPR demonstrated significant protective effects against glutamate-induced excitotoxicity in PC12 cells, evidenced by increased cell viability and reduced intracellular oxidative stress. Further proteomic analysis revealed that peptide KAPGLLPR significantly affected the key proteins such as GPX4 (antioxidant), Usp15, and Casp9 (pro-apoptotic). This study not only identifies a novel cognition-enhancing peptide from CH but also elucidates its neuroprotective mechanism, providing a new strategy for exploring and developing CH-based therapeutics.