The class B G protein-coupled receptors (GPCRs), glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R), have key roles in glucose homeostasis and therefore represent valuable drug targets for diabetes. Zhang et al. now report the crystal structure of the full-length human GCGR in an inactive conformation in complex with a negative allosteric modulator (NAM) and an antigen-binding fragment of an inhibitory antibody. A 12-residue segment termed 'the stalk' is shown to adopt a β-strand conformation and interact with extracellular loop 1 (ECL1), which forms a compact β-sheet structure. Both the stalk and ECL1 are found to have critical roles in modulating peptide ligand binding and receptor activation. Meanwhile, Song et al. present crystal structures of the human GLP1R transmembrane domain in complex with two different NAMs, revealing a common binding site located outside helices 5–7 near the intracellular part of the receptor. In the NAM-bound GLP1R, movement of helix 6 away from helix 7 — implicated to be required for G protein coupling — is restricted. Molecular dynamics simulations indicate that positive allosteric modulators target the interface between helices 5–6, which induces a conformational change.