Sodium is a prominent prognostic biomarker for assessing health status. An imbalance in sodium concentration, known as dysnatremia, is considered one of the most prominent predictors for mortality and morbidity in hospitalized patients and patients in intensive care units (ICUs). Dysnatremia possesses a clinical challenge leading to adverse health complications including cardiovascular diseases, Coronavirus (COVID-19), and chronic kidney diseases. Using biosensors for online sodium monitoring can be a promising approach to overcome this condition. In this regard, biosensors based on field-effect transistors (FETs) have promising advantages, including high sensitivity, quick response, and easy fabrication. Most of the currently developed FET designs are used only for sensing sweat and in-vitro blood/interstitial fluids (ISF). Using ISF for online detection of biomarkers and long-term health monitoring with FETs has not yet been fully resolved. Herein we propose an innovative stretchable skin-conformal fast-response microneedle extended-gate FET (MN-EGFET) biosensor for real-time detection of sodium in the ISF for minimally invasive health monitoring along with high sensitivity, low limit of detection, excellent biocompatibility, and on-body mechanical stability. This platform can, furthermore, be integrated with wireless-data transmitter and the Internet-of-Things (IoT) cloud for real-time monitoring and long-term analysis and can potentially serve as a health analyzer to monitor an individual’s health status, showing great potential for home healthcare and clinical diagnosis.