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To evaluate the antioxidant activity and the characteristics of hydrolysate from gastrointestinal digestion (in vitro simulated gastric, intestinal digestion) of filefish Navodon septentrionalis skin protein, the antioxidant activity of digestive products (reducing power, OH radical-scavenging rate, O-2 radical-scavenging rate, DPPH· radical-scavenging rate) and product characteristics (amino acids composition, molecular weight distribution) were analyzed. The results showed that: the antioxidant characteristics of amino acids of the fish skin protein was rich in 29.6%; the substrate concentration was 8 mg/mL, the hydrolysate had higher antioxidant activity; the antioxidant peptides produced mainly in the simulated duodenal digestion phase, DPPH radical-scavenging rate was 83.29%, and in this phase, seven more kinds of free amino acids in the product were found than those of raw materials. All kinds of free amino acid content were increased significantly, at the same time, molecular peptides product weight distribution concentrated in the 200～5 000 Da, and the main peptides were at 2 152 Da and 1 352 Da which might be responsible for its antioxidant activity. The oligopeptide fraction of molecular size of 200~5 000 Da, revealed the highest potential capacity to scavenge free radicals and binding irons. It appears as promising ingredient to formulate functional foods with antioxidant activity.