Abstract: This study aimed to investigate the effect of commercial protease enzymolysis and in vitro simulated gastrointestinal digestion on the release of ACE inhibitory peptides from the defatted goat milk powder with high digestibility, and to evaluate the necessity and the extent of enzymatic hydrolysis. Neutrase, alcalase, protamex, and flavourzyme were used for the enzymolysis of the defatted Kuishan goat milk powder. The goat milk and its enzymatic hydrolysates were further digested via simulated gastrointestinal digestion in vitro. The peptide content, ACE inhibitory activity and molecular weight distribution of the enzymatic hydrolysates and the simulated gastrointestinal digests were determined. Results showed that after the simulated gastrointestinal digestion in vitro, the peptide content and ACE inhibitory activity of the goat milk powder digests were 20.81 mg/mL and 62.55%, respectively. However, after moderate enzymatic hydrolysis by alcalase and flavourzyme, the peptide content and ACE inhibitory activity of simulated gastrointestinal digests decreased. After moderate enzymolysis by protamex, the peptide content and ACE inhibitory activity of simulated gastrointestinal digests were increased slightly to 22.67 mg/mL and 69.29%, respectively. After moderate enzymolysis by neutrase, the peptide content and ACE inhibitory activity of simulated gastrointestinal digests were significantly increased to 23.76 mg/mL and 81.10%, respectively. The molecular weight (MW) distribution results showed that after in vitro simulated gastrointestinal digestion, the amount of the small molecular peptides with MW<1000 Da increased from 70.77% to 90%. Above results indicate that Kuishan goat milk powder can exert ACE inhibitory activity after gastrointestinal digestion, and the ACE inhibitory activity can be further increased by 28.83% after neutral protease hydrolysis to degree of hydrolysis of 8%. Therefore, it was necessary to further enzymatic hydrolysis to a certain extent.