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Inflammatory bowel disease (IBD) has become alarmingly prevalent in the last two decades affecting 6.8 million people worldwide with a starkly high relapse rate of 40% within 1 year of remission. Existing visual endoscopy techniques rely on subjective assessment of images that are error-prone and insufficient indicators of early-stage IBD, rendering them unsuitable for frequent and quantitative monitoring of gastrointestinal health necessary for detecting regular relapses in IBD patients. To address these limitations, we have implemented a miniaturized smart capsule (2.2 cm × 11 mm) that allows monitoring reactive oxygen species (ROS) levels as a biomarker of inflammation for quantitative and frequent profiling of inflammatory lesions throughout the gastrointestinal tract. The capsule is composed of a pH and oxidation reduction potential (ORP) sensor to track the capsule's location and ROS levels throughout the gastrointestinal tract, respectively, and an optimized electronic interface for wireless sensing and data communication. The designed sensors provided a linear and stable performance within the physiologically relevant range of the GI tract (pH: 1–8 and ORP: −500 to +500 mV). Additionally, systematic design optimization of the wireless interface electronics offered an efficient sampling rate of 10 ms for long-running measurements up to 48 h for a complete evaluation of the entire gastrointestinal tract. As a proof-of-concept, the capsule the capsule's performance in detecting inflammation risks was validated by conducting tests on in vitro cell culture conditions, simulating healthy and inflamed gut-like environments. The capsule presented here achieves a new milestone in addressing the emerging need for smart ingestible electronics for better diagnosis and treatment of digestive diseases.