Protein engineering of alternative protein scaffolds is an emerging field having applications ranging from developing assay tools and imaging reagents all the way to approved drugs. Based on their size, shape and chemical properties, they can provide the proper attributes in specific areas where antibodies or small molecules fail to do so. Chagasin is a cysteine protease inhibitor from the protozoan parasite Trypanosoma Cruzi that comprises an Ig-like fold, where three loops on the same side of the molecule mediate protein-protein interactions to bind to the active site of the protease. Chagasin also has relatively high thermal stability, despite not having any disulfide bonds. This feature provides additional favorable properties as a scaffold since chagasin could be used to target both extra- and intracellular proteins. Here, we engineered chagasin as an alternative protein scaffold to generate specific binders against selected protein targets using phage display. We successfully generated functional binders against the Wnt pathway receptor LRP6 as well as the growth factor VEGF. The engineered variants have high affinity for their respective targets and potent inhibitory activity in their respective cellular assays. The rapid generation of high affinity and functional binders as well as the simple production of chagasin variants in E. coli makes it a useful molecular tool to study biological pathways and validate potential drug targets.