Hydrogen sulfide (H2S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H2S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H2S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas-sensing ingestible capsule is developed to enable real-time, wireless amperometric measurement of H2S in GI conditions. A gold (Au) three-electrode sensor is modified with a Nafion solid-polymer electrolyte (Nafion-Au) to enhance selectivity toward H2S in humid environments. The Nafion-Au sensor-integrated capsule shows a linear current response in H2S concentration ranging from 0.21 to 4.5 ppm (R2 = 0.954) with a normalized sensitivity of 12.4% ppm−1 when evaluated in a benchtop setting. The sensor proves highly selective toward H2S in the presence of known interferent gases, such as hydrogen (H2), with a selectivity ratio of H2S:H2 = 1340, as well as toward methane (CH4) and carbon dioxide (CO2). The packaged capsule demonstrates reliable wireless communication through abdominal tissue analogues, comparable to GI dielectric properties. Also, an assessment of sensor drift and threshold-based notification is investigated, showing potential for in vivo application. Thus, the developed H2S capsule platform provides an analytical tool to uncover the complex biology-modulating effects of intraluminal H2S.