Gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD), result in dilated adherens and tight junctions, altering mucosal tissue permeability. Few monitoring techniques have been developed for in situ monitoring of local mucosal barrier integrity, and none are capable of non-invasive measurement beyond the esophagus. In this work, this technology gap is addressed through the development of a noise-resilient, flexible bioimpedance sensor integrated ingestible device containing electronics for low-power, four-wire impedance measurement and Bluetooth-enabled wireless communication. Through electrochemical deposition of a conductive polymeric film, the sensor charge transfer capacity is increased 51.4-fold, enabling low-noise characterization of excised intestinal tissues with integrated potentiostat circuitry for the first time. A rodent animal trial is performed, demonstrating successful differentiation of healthy and permeable mice colonic tissues using the developed device. In accordance with established mucosal barrier evaluation methodologies, mucosal impedance was reduced between 20.3 ± 9.0% and 53.6 ± 10.7% of its baseline value in response to incrementally induced tight junction dilation. Ultimately, this work addresses the fundamental challenges of electrical resistance techniques hindering localized, non-invasive IBD diagnostics. Through the development of a simple and reliable bioimpedance sensing module, the device marks significant progress towards explicit quantification of “leaky gut” patterns in the GI tract.