Diabetes is a chronic disease that has become a serious public health concern as it affects around 382 million people worldwide. Diabetic patients require multiple-dose insulin injection or pump therapy to regulate glucose concentration in the body. Our aim is to develop a self-powered, wearable sensor capable of continuously measuring glucose concentration of the interstitial fluid in subcutaneous tissue. We will also provide cytotoxicity data using in vitro and in vivo studies to assess the feasible operation of our sensor. Pilot in vivo experiments involving rats will test sensor’s selectivity, sensitivity, reversibility, and biocompatibility. We anticipate that the wearable readout device coupled with label-free optical biosensors will aid in realizing prolonged glucose monitoring systems that will advance diabetes management at clinical and point-of-care settings. These devices may provide real-time, long-term glucose measurements that can be integrated with insulin pumps to form an automated feedback loop in glycemic management.