In this study, we investigate the effect of nine noncanonical alpha,alpha-dialkyl glycines on the structure, dynamics, and membrane permeation properties of a small peptaibol, peptaibolin. The noncanonical amino acids under study are Aib (alpha-amino isobutyric acid), Deg (alpha,alpha-diethyl glycine), Dpg (alpha,alpha-dipropyl glycine), Dibg (alpha,alpha-di-isobutyl glycine), Dhg (alpha,alpha-dihexyl glycine), D Phi g (alpha,alpha-diphenyl glycine), Db(z)g (alpha,alpha-dibenzyl glycine), Ac(6)c (alpha,alpha-cyclohexyl glycine), and Dmg (alpha,alpha-dihydroxymethyl glycine). It is hypothesized that these amino acids are able to induce well-defined secondary structures in peptidomimetics. To investigate this hypothesis, we designed new peptaibolin peptidomimetics by replacing the native Aib positions with a new alpha,alpha-dialkyl glycine. We show that Dhg and Ac(6)c noncanonical amino acids are able to induce alpha-helix secondary structures of peptaibolin in water, which are not present in the native structure. We also demonstrate that the alpha,alpha-dialkyl glycines increase the membrane permeability of peptaibolin in 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) membranes. However, there is no apparent correlation between increased helicity and membrane permeability. In summary, we show that some alpha,alpha-dialkyl glycines under study induce the formation of alpha-helix secondary structures in peptaibolin and promote spontaneous membrane permeation. Our findings increase the knowledge of the membrane permeability and folding of peptides incorporating alpha,alpha-dialkyl glycines.