The cholesterol-lowering property is well documented from soybean proteins. Many studies have been performed to reveal the mechanism of action of β-conglycinin. Similarly, we have verified the hypocholesterolemic effect of some peptide fractions derived from β-conglycinin hydrolyzed for their capacity to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in vitro. Soybean β-conglycinin was isolated, chromatographed and characterized. The hydrolysis procedure of the protein was performed by pepsin/pancreatin action. Subsequently, the peptide fractions to different molecular weight were fractioned (peptides large than 50 kda, 50 to 30 kDa, 30 to 10 kDa, 10 to 3 kDa and peptides smaller than 3 kDa). The inhibition capacity procedure to HMG-CoA was performed using to HMG-CoA reductase assay. The total hydrolyzate from β-conglycinin have exerted a decreased of 86 and 78% to HMG-CoA activity when used 50 and 10 μL, respectively. All the fractions obtained from soybean protein (peptides > 50 kda, 50 to 30 kDa, 30 to 10 kDa, 10 to 3 kDa and peptides < 3 kDa) showed inhibit to HMG-CoA activity on a level over 50%. Furthermore, the fraction where had the smaller peptides (ranger < 3 kDa) showed the best effect. HMG-CoA activity was inhibiting on 88%. The fraction that has exerted the best inhibition was formed by three main peptides (peptides less than 3 kDa). Currently, our group is studying these majority peptides. We have expectation towards the identification of peptides that may present some hypocholesterolemic property, and there by advance in the elucidation of their possible mechanisms of action.