AbstractSecondary structure formation and stability are essential features in the knowledge of complex folding topology of biomolecules. To better understand the relationships between preferred conformations and functional properties of β‐homo‐amino acids, the synthesis and conformational characterization by X‐ray diffraction analysis of peptides containing conformationally constrained Cα,α‐dialkylated amino acid residues, such as α‐aminoisobutyric acid or 1‐aminocyclohexane‐1‐carboxylic acid and a single β‐homo‐amino acid, differently displaced along the peptide sequence have been carried out. The peptides investigated are: Boc‐βHLeu‐(Ac6c)2‐OMe, Boc‐Ac6c‐βHLeu‐(Ac6c)2‐OMe and Boc‐βHVal‐(Aib)5‐OtBu, together with theC‐protected β‐homo‐residue HCl·H‐βHVal‐OMe. The results indicate that the insertion of a βH‐residue at position 1 or 2 of peptides containing strong helix‐inducing, bulky Cα,α‐disubstituted amino acid residues does not induce any specific conformational preferences. In the crystal state, most of the NH groups of β‐homoresidues of tri‐ and tetrapeptides are not involved in intramolecular hydrogen bonds, thus failing to achieve helical structures similar to those of peptides exclusively constituted of Cα,α‐disubstituted amino acid residues. However, by repeating the structural motifs observed in the molecules investigated, a β‐pleated sheet secondary structure, and a new helical structure, named (14/15)‐helix, were generated, corresponding to calculated minimum‐energy conformations. Our findings, as well as literature data, strongly indicate that conformations of βH‐residues, with theµtorsion angle equal to