The ion-sensitive field-effect transistor (ISFET) is a well-established electronic device mainly used for pH sensing. However, its potential to detect other biomarkers in easily accessible biologic fluids with high accuracy and dynamic range is still an area of active research. In this study, we present the modeling of an ISFET that can detect the presence of chloride ions in sweat with a limit-of-detection of 0.004 mol/m 3 . The device is specifically designed to aid the diagnosis of cystic fibrosis, considering the interplay between the semiconductor and the electrolyte containing the ions of interest, using the finite element method. Our findings indicate that chloride ions directly interact with the hydroxyl surface groups of the gate oxide and replace protons previously adsorbed on the surface. The results suggest that this device could replace traditional sweat testing in the diagnosis and management of cystic fibrosis, as it is easy-to-use, cost-effective, and non-invasive, leading to earlier and more accurate diagnoses.