Macrocyclic peptides with a head-to-tail cyclized backbone are intriguing natural products with interesting properties. A family of macrocyclic peptides named PawS-Derived Peptides (PDPs) is produced from precursors of seed storage albumins in species of the sunflower family. Un unusual member is PDP-23 from Zinnia elegans, which at 28 amino acids and with two disulfide bonds is twice size of typical PDPs. We produced PDP-23 by solid phase peptide synthesis and used two-dimensional solution NMR spectroscopy to elucidate its structural features. It adopts a unique structure in which two β-hairpins, each stabilized by one of the disulfide bonds, are connected by turns that act as hinges. In water two PDP-23 molecules form a symmetric dimer enclosing a hydrophobic core, while addition of organic co-solvent results in a monomeric clam-shaped tertiary structure, and in the presence of micelles the clam opens up allow insertion of hydrophobic residues into the micelle. Chemical synthesis of the mirror image d-PDP-23 allowed us to confirm the dimeric structure using racemic crystallography. An ability to alter structure based on environment may offer advantages over more rigid disulfide-rich scaffolds in drug development and we have demonstrated this by conjugating a rhodamine dye to PDP-23 to create a stable, cell permeable inhibitor of the P-glycoprotein drug efflux pump, which is upregulated in many chemo resistant cancer cells.