Analyses of high resolution crystal structures have shown that antibody hypervariable loops L1, L2, and L3 from the light chain, as well as H1 and H2 from the heavy chain, can be assigned to only a small family of canonical conformations. We describe here attempts to generate structural mimetics of L2, L3, and H2 canonical conformations, which are beta-hairpin structures connecting adjacent antiparallel beta-strands. The five mimetics studied comprise cyclic peptides, in which the CDR loop has been transplanted from the immunoglobulin framework onto a D-Pro-L-Pro template. Their preferred conformations have been studied by NMR and MD with time-averaged, NOE-derived distance restraints. The results show that accurate mimetics of L3 and H2 loops can be obtained, whereas the L2 canonical conformation, which appears to be inherently strained, could not be mimicked in this way. For example, an eight-residue L3 loop from antibody HC19 attached to the D-Pro-L-Pro template adopts not only a backbone hairpin conformation but also aromatic-aromatic T-stacking interactions between tryptophan side-chains, that are essentially identical to those in the antibody crystal structure. This straightforward and effective approach to hairpin design may be of great value for generating small molecule mimetics of hairpin loops on proteins of diverse function.