Ion channel-modulating drugs play an important role in treating cardiovascular diseases. Facing the demands for continuous monitoring of drug effectiveness, the conventional techniques have become limited when investigating a long-term cellular physiology. To address the challenge, we propose a drug-screening platform using the stretch-out electrical double layer (EDL)-gated field-effect transistor-based biosensors (BioFETs). In this work, BioFETs were utilized to amplify electrophysiological signals from the mammalian cardiomyocytes (H9c2). The stretch-out configuration avoided a chemical corrosion on FETs and prolonged the lifetime of a BioFET system. A physical model is presented to elucidate the signal response to a drug effect on a cell. Fibronectin and gelatin were coated on sensors and served as the adhesive layers where H9c2 cells attached. BioFETs demonstrated an ability to qualitatively distinguish a depolarization and a polarization of the cytomembranes. The signal responses to the changes of transmembrane potentials were monitored in real-time, and they were highly correlated. The effects of nifedipine and calcium ions on cellular electrophysiology were examined and discussed. Due to the capability of a rapid detection, a prolonged lifetime, and an excellent sensitivity to an electrical change, a stretch-out EDL-gated BioFET can be a drug-screening platform for ion channel modulators.