Abstract: To explore the antioxidant activity of ready-to-eat sea cucumber—a mainstream commercial product—following digestion, this study first characterized the nutritional composition of ready-to-eat sea cucumber, and focused on analyzing the antioxidant activity of its protein after in vitro simulated oral-gastrointestinal digestion. Finally, the mechanism of action of antioxidant peptides was explored through molecular docking. The results showed that the primary nutritional component of ready-to-eat sea cucumber was protein (69.52%), of which 67.02% was collagen. Following in vitro simulated digestion, the degree of hydrolysis of body wall protein was 75.69%. Three peptide fractions within different molecular weight (MW) exhibited concentration-dependent increases in antioxidant capacity. Notably, the fraction with MW <3 kDa displayed significantly higher ABTS⁺· scavenging activity and ferrous ion chelating capacity even at low concentrations, and the proportion of essential amino acids was significantly higher than other fractions (P<0.05). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to identify fractions with MW <3 kDa, and 36 peptides were selected for subsequent analysis following screening. Molecular docking results indicated that all peptides could activate the Keap1-Nrf2-ARE signaling pathways via occupying the site of Nrf2 within Keap1’s pocket, with hydrogen bonding and hydrophobic interaction being the primary forces. These findings confirm that ready-to-eat sea cucumber maintains its antioxidant capacity after in vitro simulated oral-gastrointestinal digestion, supporting its potential use as a dietary antioxidant source.