Sunflower trypsin inhibitor-1 (SFTI-1) is a backbone cyclic peptide naturally found in the seeds of the common sunflower and is a potent inhibitor of trypsin. The structure of SFTI-1 comprises 14 residues that form a β-sheet conformation, stabilised by a single disulfide bond.1 This highly rigid structure engenders exceptional enzymatic and thermal stability,2 making it an attractive template for peptide engineering in drug design applications. In our work, we have capitalised on this unique peptide for two separate drug design applications: targeting therapeutically relevant proteases and G-protein coupled receptors. In the first application, we have focused on the synthesis of triazole-bridged disulfide mimetics in engineered SFTI-1 derivatives, targeting the serine proteases kallikrein related peptidase-7, plasmin and matriptase. In the second application, we have implemented a ‘grafting’ strategy, in which a small pharmacophore is inserted into the framework of SFTI-1, leading to pM and selective melanocortin receptor-1 agonists with potential application in the treatment of melanoma.3