Caveolin-1 is a target for academic and pharmaceutical research due to its many cellular roles and associated diseases. We report peptide WL47 (1), a small, high-affinity, selective disrupter of cavolin-1 oligomers. Developed and optimized though screening and analysis of synthetic peptide libraries, ligand 1 has 7500-fold improved affinity compared to its T20 parent ligand, and an 80% decrease in sequence length. Ligand 1 will permit targeted study of caveolin-1 function.