Bioactive peptides have a positive impact on body functions and conditions and may influence health. However, peptides are degraded by digestive enzymes, such as pepsin in the stomach when ingested orally. In order to solve this problem, we previously focused on porous silica gel and found that by using calcined silica gel, hydrophobic and negatively charged peptides could be efficiently delivered into the intestine, because peptides adsorbed on the cavity of the silica gel could be protected from enzymatic degradation. Therefore, in this study, we attempted to develop peptides whose physicochemical properties were suitable for intestinal delivery without lowering their activity. We also proposed guidelines of predictive selection of such peptides. For that purpose, we selected hypercholesterolemic peptides as a model and re-designed the peptides based on the previously reported color map, in which intestinal delivery degree was predictively depicted as contour lines. As a result, we succeeded in getting five different re-designed peptides from 1265 substituted peptide derivatives. These peptides showed a dual function of being suitable for intestinal delivery with silica gel and for disruption of bile acid micelles. The release amount of IYEYMY was 2.09 times the parent peptide, which was the highest. (C) 2019, The Society for Biotechnology, Japan. All rights reserved.