Specific interactions between cations and proteins have a strong impact on peptide and protein structure. Herein, we shed light on the nature of the underlying interactions, especially regarding effects on the polyamide backbone structure. This was done by comparing the conformational ensembles of model peptides in isolation and in the presence of either Li+ or Na+ by using state-of-the-art density-functional theory (including van der Waals effects) and gas-phase infrared spectroscopy. These monovalent cations have a drastic effect on the local backbone conformation of turn-forming peptides, by disruption of the hydrogen-bonding networks, thus resulting in severe distortion of the backbone conformations. In fact, Li+ and Na+ can even have different conformational effects on the same peptide. We also assess the predictive power of current approximate density functionals for peptide–cation systems and compare to results with those of established protein force fields as well as high-level quantum chemistry calculations (CCSD(T)).