Semiconducting polymers are very promising materials for biomedical application, thanks to the ability to conduct both ions and electrons, their biocompatibility and their flexible and soft mechanical properties. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has high conductivity, electrochemical and thermal stability in aqueous environment and low oxidation potential that renders it suitable as smart nano-interface with biological elements and environment. In our work, we present PEDOT:PSS-based Organic Electrochemical Transistors (OECTs) for the electrical continuous monitoring of tissue culture viability, growth and stress response induce by drug treatment, providing an alternative and real-time way to standard optical evaluation techniques, which often require complex instrumentation and laboratory protocols. In OECTs, the electronic current flowing in the conducting polymer channel is modulated by the ionic current crossing the interface with an electrolyte solution (cell culture medium). The presence of a cell monolayer, directly grown on the semiconducting channels and gates of our devices, slow down the ions flowing in the conducting polymer, thus giving an electronic readout of the layer integrity and health. Moreover, the transistor configuration enhances the sensitivity due to amplification of the ionic current. Finally, changing the dimensions of the device and switching between its two configurations, renders it suitable for different kind of cells, allowing even the study of leaky-barrier or non-barrier cell lines. We demonstrated that our devices provide a simple, low-cost and dynamic method to monitor cell viability and reactions to toxic agents of CaCo-2 and NIH-3T3 cell lines, paving the way for high throughput and low-cost screening of drug discovery or toxicology.