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In this paper, alkali protease was used to enzymatically hydrolyze wheat germ proteins grown in the Hetao region. A univariate analysis and an orthogonal experiment were conducted to optimize the enzymatically hydrolyze process conditions of wheat germ proteins, with the degree of hydrolysis taken as the indicator. Moreover, the in vitro hypolipidemic effect of wheat germ polypeptides was investigated. The results showed that the degree of hydrolysis of wheat germ proteins was 37.18%±0.25% achieved by the following conditions, substrate concentration of 6.0%, temperature at 50 ℃, pH of 10.5 and protease amount of 12000 U/g. When the concentration of wheat germ polypeptides was 5 mg/mL, the rate of inhibiting cholesterol solubilisation into micelles was 27.11%±0.36%, the pancreatic lipase activity inhibition rate was 33.54%±0.57%, and cholesterol esterase activity inhibition rate was 38.13%±0.29%. Moreover, after ultrafiltration, the relative molecule weight of polypeptides less than 1 kDa accounted for 54.30%±0.32% of all polypeptides, indicating that low-molecular-weight wheat germ polypeptides might yield superior hypolipidemic effects. The work provides a theoretical foundation for further exploring the mechanism between Hetao wheat germ polypeptides and hypolipidemic effect.