AbstractLiving cells possess a variety of transmembrane signaling systems that receive chemical and physical cues from the environment and transduce this information into an intracellular signal that triggers downstream cellular responses. This Review aims to present recent advances in the design of bioinspired systems that mimic transmembrane signaling in synthetic and living cells. We summarize the building of cell-like membranous structures and the construction of interfacial recognition between chemical or biological components. After introducing two main mechanisms of signal transduction in biology through receptor tyrosine kinase and G‐protein coupled receptors, we then highlight the possibility of mimicking transmembrane signaling with transducer integrated systems. We survey the potential for applying supramolecular materials (e.g., DNA origami, polypeptide structures and polymer scaffolds) to interact with surface receptors on the plasma membrane, providing an avenue for the application of therapeutics.