This review discusses the signal transduction interfaces in field-effect transistor (FET)-based biosensors, which are crucial for translating electrochemical reactions into output signals. The interfaces are categorized into chemically synthesized, physically structured, and biologically induced types. Chemically synthesized interfaces, such as ion-sensitive membranes (ISMs) and molecularly imprinted polymers (MIPs), are designed to transduce interactions between chemicals and charged ions or biomolecules into electrical signals. Physically structured interfaces, like polymeric nanofilters, enhance signal-to-noise ratios by trapping interfering species while allowing target molecules to reach the detection surface. Biologically induced interfaces, such as living cells and enzymes, provide high specificity and selectivity but have limitations in terms of stability and cost. The review highlights the importance of these interfaces in controlling biosensing parameters such as specificity, selectivity, binding constant, limit of detection, signal-to-noise ratio, and biocompatibility. It also discusses the challenges and advancements in developing these interfaces for wearable biosensors and in vitro diagnostics.This review discusses the signal transduction interfaces in field-effect transistor (FET)-based biosensors, which are crucial for translating electrochemical reactions into output signals. The interfaces are categorized into chemically synthesized, physically structured, and biologically induced types. Chemically synthesized interfaces, such as ion-sensitive membranes (ISMs) and molecularly imprinted polymers (MIPs), are designed to transduce interactions between chemicals and charged ions or biomolecules into electrical signals. Physically structured interfaces, like polymeric nanofilters, enhance signal-to-noise ratios by trapping interfering species while allowing target molecules to reach the detection surface. Biologically induced interfaces, such as living cells and enzymes, provide high specificity and selectivity but have limitations in terms of stability and cost. The review highlights the importance of these interfaces in controlling biosensing parameters such as specificity, selectivity, binding constant, limit of detection, signal-to-noise ratio, and biocompatibility. It also discusses the challenges and advancements in developing these interfaces for wearable biosensors and in vitro diagnostics.