Hemp seeds have a long history as a foodstuff and are traditionally associated with longevity in China. In this study, the simulated digestion of hemp seed protein (HSP) was investigated to evaluate its health benefits. After digestion, a higher degree of hydrolysis, elevated DPPH and ABTS radical-scavenging activities, and enhanced FRAP reducing power were observed, reflecting the digestibility and antioxidant potential of HSP. Moreover, the HSP digest improved HepG2 cell viability under H2O2-induced oxidative stress. Peptidomic analysis identified 1101 peptides (75 % < 1 kDa), among which 89 were predicted to be bioactive. From these, 27 water-soluble, non-toxic peptides were further examined. Molecular docking showed that most peptides had stronger binding affinities to ABTS, DPPH, and Keap1 than glutathione. A 100-ns molecular dynamics simulation further confirmed the antioxidant potential of the peptides, highlighting HSP digest as a promising source of antioxidant peptides with direct radical-scavenging activity and potential Nrf2-pathway activation.