Biological cells use cations as signaling messengers to regulate a variety of responses. Linking cations to the functionality of synthetic membranes is thus crucial to engineering advanced biomimetic agents such as synthetic cells. Here, we introduce bioinspired DNA-based receptors that exploit noncanonical G-quadruplexes for cation-actuated structural and functional responses in synthetic lipid membranes. Membrane confinement grants cation-dependent control over receptor assembly and, when supplemented with hemin cofactors, their peroxidase DNAzyme activity. Cation-mediated control extends to receptor lateral distribution to localize DNA-based catalysis within phase-separated membrane domains of model synthetic cells, imitating the localization of multimeric membrane complexes to signaling hubs in living cells. Our modular strategy paves the way for engineering from the bottom-up cation-responsive pathways for sensing, signaling, and communication in synthetic cellular systems.