Effective peptidomimetics should posses structural rigidity and appropriate interaction pattern leading to potential spatial and electronic matching to the target receptor site. Rational design of such small bioactive molecules could push chemical synthesis and molecular modeling toward faster progress in medicinal chemistry. Conformational properties of N-t-butoxycarbonyl-glycine-(E/Z)-dehydrophenylalanine N′,N′-dimethylamides (Boc-Gly-(E/Z)-ΔPhe-NMe2) in chloroform were studied by NMR and IR spectroscopy. The experimental findings were supported by extensive calculations at DFT(B3LYP, M06-2X) and MP2 levels of theory and the β-turn tendency for both isomers of the studied dipeptide were determined in vacuum and in solution. The theoretical data and experimental IR results were used as an additional information for the NMR-based determination of the detailed solution conformations of the peptides. The obtained results reveal that N-methylation of C-terminal amide group changes dramatically the conformational properties of studied dehydropeptides. Theoretical conformational analysis reveals that the tendency to adopt β-turn conformations is much weaker for the N-methylated Z isomer (Boc-Gly-(Z)-ΔPhe-NMe2), both in vacuum and in polar environment. On the contrary, N-methylated E isomer (Boc-Gly-(E)-ΔPhe-NMe2) can easily adopt β-turn conformation, but the backbone torsion angles (φ1, ψ1, φ2, ψ2) are off the limits for common β-turn types. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 28–40, 2014.