AbstractOral drug administration provides a convenient and patient‐compliant way for drug delivery, especially for chronic diseases and prolonged pharmacological treatments. However, due to the repetitiveness of such therapeutic approach, the patients are led to neglect/forget the therapy affecting the healthcare delivery. Indeed, the non‐adherence to pharmacological prescriptions and the unknown amount of real‐time drug release result in a non‐compliant therapeutic drug level over the protracted therapies. The proposed technology will enable the monitoring of both pharmacological adherence and real‐time drug release. The approach exploits a passive intrabody communication (IBC) activation in order to enable an edible pill, realized starting from food additives and food‐grade materials, to monitor pharmacological adherence. Following activation, the signal is modulated by IBC coupling switching triggered by pill degradation in a gastrointestinal tract, resulting in a monitored drug release. The proof‐of‐concept is designed for a targeted release and monitoring of Metformin in the intestine. The system shows an in vitro limit of cumulative drug release detection of 18 µg mL−1 and a limit of real‐time drug release detection of 2 µg mL−1 min−1. This platform represents the first solution to monitor passive drug release in real‐time, from intake to complete absorption, enabling unique and long‐sought healthcare therapy and treatment opportunity.