Simultaneous monitoring of diverse salivary parameters can reveal underlying mechanisms of intraoral biological processes and offer profound insights into the evolution of oral diseases. However, conventional analytical devices with bulky volumes, rigid formats, and discrete sensing mechanisms deviate from the requirements of continuous biophysiological quantification, resulting in huge difficulty in precise clinical diagnosis and pathogenetic study. Here, we present a flexible hybrid electronic system integrated with functional nanomaterials to continuously sense Ca ²⁺ , pH, and temperature for wireless real-time oral health monitoring. The miniaturized system with an island-bridge structure that is designed specifically to fit the teeth is only 0.4 g in weight and 31.5 × 8.5 × 1.35 m m 3 in dimension, allowing effective integration with customized dental braces and comfort attachment on teeth. Characterization results indicate high sensitivities of 30.3 and 60.6 mV/decade for Ca ²⁺ and pH with low potential drifts. The system has been applied in clinical studies to conduct Ca ²⁺ and pH mappings on carious teeth, biophysiological monitoring for up to 12 h, and outcome evaluation of dental restoration, providing quantitative data to assist in the diagnosis and understanding of oral diseases. Notably, caries risk assessment of 10 human subjects using the flexible system validates the important role of saliva buffering capacity in caries pathogenesis. The proposed flexible system may offer an open platform to carry diverse components to support both clinical diagnosis and treatment as well as fundamental research for oral diseases and induced systemic diseases.