Organic electrochemical transistors (OECTs), as an important functional device in the field of organic bioelectronics, show a great potential for applications in neuromorphic computing, biosensing, and logic circuits due to their unique advantages of high transconductance, low operating voltage, and good biocompatibility. Relied on the rapid development of organic mixed ionic-electronic conductors (OMIECs), the device performance of OECTs has been significantly improved, thus promoting diversified applications. In this article, we introduce the working mechanism and device parameters of current OECTs, and review the advances in molecular design strategies and development status of OMIECs in terms of side-chain engineering and backbone engineering. Moreover, the related research progress of p/ntype OMIECs, device performance, and applications are highlighted. Finally, the challenges and opportunities for the development and application of cost-effective and operationally stable OECTs are summarized.