Affinity-driven reactions have allowed chemists to perform site-selective modifications of native proteins. By combining the high cysteine chemoselectivity of hypervalent iodine-based ethynylbenziodoxolones (EBXs) with the site selectivity of peptide ligands known to inhibit protein−protein interactions, we achieved site-selective labeling of Cys434 in the KELCH domain of Kelch-like epichlorohydrin-associated protein 1 (KEAP1), a key protein in the regulation of oxidative stress. EBXs could be used either as traceless reagents with release of the peptide ligand to introduce reactive handles such as azides or alkynes or as covalent reagents leading to the formation of peptide−protein adducts, which could be cleaved in a separated step.