AbstractAdvanced capabilities in noninvasive, in situ monitoring of parameters related to sweat serve as the basis for obtaining real‐time insights into human physiological state, health, and performance. Although recently reported classes of soft, skin‐interfaced microfluidic systems support powerful functions in this context, most are designed as single‐use disposables. As a result, associated waste streams have the potential to create adverse environmental impacts. Here, we introduce materials and fabrication techniques that bypass these concerns through biodegradable microfluidic systems with a full range of features, including measurement of sweat rate and total loss, and colorimetric analysis of biomarkers. The key components fully degrade through the enzymatic action of microorganisms in natural soil environments, or in industrial compost facilities, to yield end products with beneficial uses as fertilizers and species to improve soil health. Detailed characterization of the constituent materials, the fabrication procedures, the assembly processes, and the completed devices reveal a set of essential performance parameters that are comparable to, or even better than, those of non‐degradable counterparts. Human subject studies illustrate the ability of these devices to acquire accurate measurements of sweat loss, sweat rate, pH, and chloride concentration during physical activities and thermal exposures.image