Biosensing of physiological signals, such as the body temperature and biomolecules, are of critical importance to disease monitoring, diagnosis, and treatment, in both clinical and research settings. Optical biosensors in particular have shown unique advantages when compared with traditional electrochemical sensors—optical sensors are electromagnetic interference (EMI) free, resistant to electroactive interferants, while exhibiting both sensitivity and specificity. Integrated photonics based on the refractive index sensing mechanism is one promising example of compact optical biosensing, with high sensitivity, specificity, and label-free operation. Moreover, these integrated photonic sensors can have ultrasmall form factors and be manufactured at low costs, thanks to their CMOS-fabrication compatibility. In the first part of the thesis, we demonstrate a rigid, silicon-on-insulator-based integrated photonic biosensor for high-sensitivity glucose detection. We show that by functionalization of receptors on a micro-ring resonator (MRR) sensor surface, the MRR sensor is able to reach the limit of detection for non-invasive glucose sensing in saliva and tears. Moreover, we show that the MRR sensor responds minimally to common interferents present in biofluids and performs stably across a wide pH range compared with enzyme-based electrochemical sensors. These results could potentially facilitate the development of a low-cost, benchtop optical platform for non-invasive diabetes screening. Although SOI-based integrated photonic sensors can detect biomolecules with a high LOD and specificity, the sensor’s mechanical rigidity has largely limited its applications to in vitro, benchtop settings. In the second part of the thesis, we demonstrate a flexible integrated photonic platform that is better suited for in vivo biological applications. We show that by utilizing TiO2 as the core material and SU-8 polymer as the flexible cladding, the flexible photonic MRR sensors are capable of high-sensitivity temperature sensing. More importantly, we show that the flexible photonic sensor can be surface-functionalized through a generalized, polymer-compatible approach for biochemical detection with sub-uM sensitivity. The successful demonstration of our sensors is a key step toward developing more biocompatible, conformal, and flexible photonic platforms for next-generation biosensing applications that require tissue contact or device implantation.