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Abstract Precision medicine requires smart, ultrasensitive, real-time profiling of bio-analytes using interconnected miniaturized devices to achieve individually optimized healthcare. Here, we report a versatile bioelectronic interface (VIBE) that senses signaling-cascade-guided receptor-ligand interactions via an electronic interface. We show that VIBE offers a low detection limit down to sub-nanomolar range characterised by an output current that decreases significantly, leading to precise profiling of these peptide hormones throughout the physiologically relevant concentration ranges. In a proof-of-concept application, we demonstrate that the VIBE platform differentiates insulin and GLP-1 levels in serum samples of wild-type mice from type-1 and type-2 diabetic mice. Evaluation of human serum samples shows that the bioelectronic device can differentiate between samples from different individuals and report differences in their metabolic states. As the target analyte can be changed simply by introducing engineered cells overexpressing the appropriate receptor, the VIBE interface has many potential applications for point-of-care diagnostics and personalized medicine via the internet of things.