Medium-sized peptides are expected as a next-generation drug discovery modality because they combine the properties of conventional small-molecule drugs and biopharmaceuticals. Nonetheless, peptides are easily degraded by digestive enzymes such as protease in the body, which could be problematic for the development of peptide-based drugs. To overcome such a problem, peptide-based foldamers containing non-proteinogenic amino acids or cyclized peptides have been reported. In addition, peptides must form stable secondary structures and their side chains should be correctly positioned to exert their bioactivity. In our lab, bioactive peptides have been developed based on regulation of secondary structures by introducing non-proteinogenic amino acids such as acyclic α,α-disubstituted amino acids (dAAs), cyclic dAAs, cyclic β-amino acids, and side-chain stapling. Based on these knowledges, I have been performing research on the development of bioactive peptides based on the secondary structural control of peptides as categorized in the following manner: (1) rational design of antimicrobial foldamers; (2) post-functionalization of helical peptides; (3) development of carrier peptides for intracellular delivery of siRNA utilizing the helical template peptides.