Despite increasing interest in peptide therapeutics within the pharmaceutical industry over the past three decades, relatively few peptides have made it through pre-clinical development to challenge the dominance of small-molecule pharmaceuticals and protein-based biologics. This is primarily due to the low membrane permeability and poor stability of linear peptides. Conversely, constrained macrocyclic peptides display enhanced stability relative to their linear counterparts and higher binding affinities due to their rigid conformation. Furthermore, macrocyclic peptides offer an effective tool to enable selective interference of the myriad of traditionally intractable proteinprotein interactions (PPIs) that mediate cellular biochemistry. Thus, this modality of therapeutic bridges the gap between the advantageous physicochemical properties of small molecules and the exceptional activity, specificity, and bioavailability inherent to protein-based biologics. While numerous synthetic methods have been developed to enable effective peptide macrocyclisation, biocompatible chemistries that work with readily accessible building blocks in environmentally acceptable solvents are still required to enable the significant impact of macrocyclic peptides as a next-generation drug discovery tool to be realised.