Achieving the therapeutic goal of treating diseases by effectively controlling the excessive accumulation of intracellular free radicals is still very challenging, which motivates researchers to develop efficient novel antioxidant peptides from sustainable resources continuously. This study first pioneered a probiotic-assisted enzymatic hydrolysis of hemoglobin, which obtained 149 peptides. Two antioxidant peptides were rapidly screened using advanced molecular dynamics simulation techniques, revealing their molecular interaction mechanisms with Keap1. It was found that GLWGKV occupied six binding sites for Keap1 to form hydrogen bonds with Nrf2, whereas LIVYPW occupied two binding sites, and the binding free energy of GLWGKV to Keap1 was lower binding more stable. Cellular experiments confirmed that GLWGKV up-regulated the expression of related proteins and increased antioxidant enzyme activities, thereby attenuating H