The G protein-coupled receptor (GPCR) family is the largest in the human genome, encoding membrane proteins that serve as the primary environmental sensors for all cells. While GPCRs are targets for approximately 25 % of prescription drugs, over 300 receptors remain untargeted, often despite clear linkage to disease. Important reasons for this are that high-throughput screening has failed to deliver optimal drug leads and a lack of structural knowledge about how ligands engage and activate GPCRs has hindered compound optimisation. Crystal structures have revealed that ligands bind GPCRs through diverse mechanisms, but new approaches are required to map ligand binding epitopes and determine the role of ligand and receptor dynamics on GPCR function. This is particularly the case for unstructured peptides, which bind their GPCRs with complex binding modes and for which there are fewer crystal structures available. NMR methods are frequently used for investigating ligand binding, protein dynamics, and for fragment based drug discovery (FBDD). NMR has not been widely applied to the study of GPCRs however, due to the challenges associated with preparing stable GPCR samples. Being integral membrane proteins, GPCRs need to be extracted from cell membranes using detergents for purification and thus the major hindrance to biochemical studies of GPCRs is that they are typically unstable in detergent micelles. To facilitate NMR studies, Cellular High-throughput Encapsulation Solubilisation and Screening (CHESS) was applied to engineer thermostabilised mutants of three prototypical GPCRs: the monoamine receptors α1A- and α1B-adrenoceptors (α1A-AR and α1B-AR); and the peptide neurotensin receptor 1 (NTS1). Here we used NMR methods to map the binding epitopes and induced receptor conformational changes that occur when neurotensin binds NTS1 and the peptide conotoxin ρ-TIa binds α1A-AR and α1B-AR. This work uncovered the complex and dynamic nature of peptide-GPCR interactions and will aid future drug design efforts.