Precise NMR structural determination of distinct hydrogen-bonded secondary folds in unnatural peptides is demonstrated by using residual dipolar couplings (RDCs), measured in organic solvent media. The results show that the conventional constraints, (3)J(HH) and NOE-derived distances alone do not allow the accurate structural elucidation even for rigid foldamers and emphasize the need of RDC-based structure validation and refinement for unnatural peptides in particular and small organic molecules in general.