A general method for sequence-specific binding of peptides remains elusive despite decades of research. By creating an array of “hydrophobically coded dimples” on the surface of surface–core doubly cross-linked micelles, we synthesized water-soluble nanoparticle receptors to recognize peptides by the location, number, and nature of their hydrophobic side chains. Minute differences in the side chains could be distinguished, and affinities up to 20 nM were obtained for biologically active oligopeptides in water.