Bioorthogonal late-stage diversification of structurally complex peptides has enormous potential for drug discovery and molecular imaging. In recent years, transition-metal-catalyzed C−H activation has emerged as an increasingly viable tool for peptide modification. Despite major accomplishments, these strategies largely rely on expensive palladium catalysts. We herein report an unprecedented cobalt(III)-catalyzed peptide C−H activation, which enables the direct C−H functionalization of structurally complex peptides, and sets the stage for a multicatalytic C−H activation/alkene metathesis/hydrogenation strategy for the assembly of novel cyclic peptides. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim