Elevated concentrations of cholesterol in plasma are associated with increased risk for heart diseases in humans. Bioactive peptides can be considered as an option to prevent or treat this condition. Currently, there are wide sources of bioactive peptides with hypocholesterolemic activities; however, most researches are focused in bioactive peptides derived from soybean and milk protein. Although there are several preparation methods for these peptides, it is a novel process to prepare bioactive peptides by genetic engineering techniques. In this review, after a general introduction on approaches and advances in bioactive peptides, recombinant strategies to generate hypocholesterolemic peptides and their purification are discussed as well as their application in food and drug design.