α,α-Disubstituted α-amino acids (dAAs), in which the α-hydrogen of the α-amino acid is replaced with an alkyl substituent, stabilize peptide secondary structures and have been utilized as a tool for building blocks of peptide foldamers. Peptides composed of acyclic dAAs with two bulky substituents equal to or larger than ethyl groups are more likely to form an extended planar conformation, whereas peptides with cyclic dAAs are more likely to adopt a helical structure. Based on these conformational properties of dAA-containing peptides, we developed a novel methodology using cyclic dAAs with an acetal side chain for conformational changes in peptides from a helical to a random structure with acidic treatment. Furthermore, peptide foldamers containing dAAs are useful for the design of functional peptides. In addition to the stabilization properties of peptide secondary structures, peptides foldamers exhibit resistance to degradation by proteases and thus are expected to be useful for development into bioactive peptides. In this presentation, I introduce cell-penetrating peptide foldamers as an application for dAAs in functional peptides. Peptide foldamers with appropriate functional groups at target positions show excellent, continuous cell membrane permeability and the ability to deliver biomacromolecules, such as plasmid DNA, into cells efficiently.