As one of the most important and novel environmental friendly energy conversion materials, thermoelectric (TE) materials can directly achieve the conversion between thermal energy and electrical energy. Currently, with the increasing human demand for flexible electronic products, organic TE materials can bring new opportunities for the development of TE devices. Conducting polymers have the advantages of rich sources, low cost, good mechanical flexibility, and easy processing, etc. Indeed, conducting polymers have been studied for more than 40 years, but they did not attract much attention because of their poor TE performance before 2000. In 2008, the ZT value of poly(3,4-ethylenedioxythiophene) (PEDOT) was firstly reported to exceed 10−3, bringing a new dawn for the development of high-performance organic TE materials. Since then, a large number of new technologies and methods have been applied to enhance the TE performance of PEDOT. In the past ten years, we have witnessed the rapid increase of PEDOT’s ZT value from 10−3 to 10−1, making PEDOT-based materials one of the most promising organic TE materials. In this review, we focus on the development of PEDOT for TE application. The comprehensive insights into the strategies and mechanisms for optimizing the TE performance of PEDOT are discussed. We have also summarize the fabrication/assembly technique, configuration, and device performance of PEDOT-based TE generator. Hopefully, this review will inspire further studies to improve the TE performance of PEDOT.