Abstract: The lipid of fish may undergo obvious oxidation and produce harmful aldehydes during digestion. In this paper, the effects of aldehyde dehydrogenase (ALDH) extract of an antioxidant yeast on fat oxidation during simulated digestion of fish were studied by taking fat peroxidation value (POV), thiobarbituric acid reactant value (TBARS), aldehyde compounds and polyunsaturated fatty acids as evaluation indexes. The results showed that in the process of simulating gastrointestinal digestion, the POV of control fish (CK) increased from (0.12±0.06) meq/kg to (1.14±0.12) meq/kg during simulated digestion. The POV of fish (free enzyme, FE) added with ALDH extract was (0.69±0.08) meq/kg after simulated digestion for 5 hours, while the POV of fish meat (embedded enzyme, EB) embedded with ALDH was (0.13±0.06) meq/kg. The TBARS value of CK group increased from (0.77±0.11) mg/kg to (2.31±0.13) mg/kg, while the TBARS values of FE and EB groups were (0.79±0.09) mg/kg and (0.19±0.09) mg/kg, respectively. Aldehydes with high content in digestive products include nonanal, hexanal, 2-heptanal, nonadienal, 2-hexenal, etc. The aldehyde content of CK group increased rapidly and significantly during digestion, while that of FE and EB group decreased gradually. At the end of digestion, the contents of hexanal, nonanal and 2-heptanal were lower than the detection limit. The oxidative losses of EPA and DHA in fish meat in CK group were 59% and 58%, 35% and 32% in FE Group and 20% and 26% in EB group. This study proves that antioxidant yeast enzyme extract can well inhibit the fat oxidation of fish during simulated digestion and effectively reduce the harmful substances produced by fat oxidation. Yeast enzyme extract may be a new active agent to control postprandial oxidative stress caused by lipid oxidation.