Bioelectronics which bridge the gap between conventional electronics and biological systems are actively researched due to their fascinating perspectives in healthcare and other fields. A key element of future bioelectronics is the organic electrochemical transistor (OECT) that, by employing a mixed ion-electron conducting materials, can perform switching tasks in electrolytic environments and serve as sensoric or actoric element. OECTs differ substantially from their inorganic field-effect counterparts, mainly due to their electrochemical, rather than electrostatic, gate operation principle. However, the working mechanism of OECTs is modeled as the one of the field-effect transistor: this approach not only fails to give quantitative agreement with experimental observation but also ignores the material properties of the channel and the chemical dynamics that stem for the operation of the device. Here, we present a new comprehensive unified model that can explain the behavior of OECTs across a broad range of materials, designs, and operation regimes. We treat the polymeric channel as a thermodynamic binary system and show that the entropy of mixing is the major driving force behind the operation of the OECT. We are able to quantify the entropic and enthalpic interactions between charged species for a variety of materials and solvents and harness this knowledge to provide guidelines for material modeling and insights for device fine-tuning for targeted applications. Finally, our thermodynamic model provides a description of the intrinsic origin of the ubiquitous hysteretic behavior of OECTs.