We introduce a new and highly efficient synthetic protocol towards multifunctional fluorescent cyclopeptides by solid-phase peptide macrocyclization via dipyrrin construction, with full scope of proteinogenic amino acids and different ring sizes. Various bicyclic peptides can be created by dipyrrinbased crosslinking and double dipyrrin-ring formation. The embedded dipyrrin can be either transformed to fluorescent BODIPY and then utilized as cancer-selective targeted protein imaging probe in vitro, or directly employed as a selective metal sensor in aqueous media. This work provides a valuable addition to the peptide macrocyclization toolbox, and a blueprint for the development of multifunctional dipyrrin linkers in cyclopeptides for a wide range of potential bioapplications.Conformationally constrained macrocyclic peptides [1] possessing larger target-selective binding surfaces of higher affinity, [2] ameliorated cell permeability and stability, [3,4] and versatile and remarkable pharmacological properties [5] compared with their linear counterparts have emerged as novel and promising molecular platforms for efficaciously modulating disease-relevant protein-protein interactions (PPIs)known therapeutic targets or those previously thought to be "undruggable". [6] To this end, a repertoire of peptide macrocyclization and stapling approaches has been developed and diversified over the past decade. [7] Cross-couplings, [8] click reactions, [9] C À H activations/functionalizations, [10] ring-closing olefin metathesis reactions, [11] Diels-Alder cycloaddi-