<p>Cell-based biosensors are evolving as versatile tools for biological research, drug development, and environmental monitoring. Living cells are used to detect elements in these biosensors, which offer significant advantages over standard transducers. The purpose of this review article is to provide an in-depth overview of cell-based biosensors, emphasizing their working principles, fabrication processes, and applications. The potential of living cells to respond to particular analytes or stimuli supports the design and operation of cell-based biosensors. Real-time and label-free identification can be accomplished by combining these cells with transducers like microelectrodes or optical sensors. Genetically engineered cells or changed microenvironments can be used in cell-based biosensors to improve performance by optimizing cell types for increased dynamic range, sensitivity, and selectivity. Cell-based biosensors are developed by meticulously cultivating and immobilizing cells on transducer surfaces while retaining their vitality and performance. Cell-based biosensors have a wide range of applications, including monitoring the environment, healthcare, and pharmaceutical research. These biosensors have been used to detect diseases, toxic substances, pollutants, and therapeutic drug screening. Cell-based biosensors are cutting-edge technology that brings together the capabilities of live cells and transducers to detect analytes in a sensitive and specific manner. These biosensors illustrate the tremendous potential for upcoming uses in healthcare and monitoring environmental conditions with further developments in fabrication methods and the inclusion of artificial intelligence.</p> Graphical Abstract <p></p>