This study presents a novel approach to enhance the thermoelectric performance of flexible PEDOT:PSS fibers through a triple post-treatment process involving concentrated sulfuric acid (H₂SO₄), sodium borohydride (NaBH₄), and 1-ethyl-3-methylimidazolium dichloroacetate (EMIM:DCA). The optimized fibers exhibit a high power factor of (55.4 ± 1.8) μW m⁻¹ K⁻² at 25 °C, significantly improving upon the original PEDOT:PSS properties. The post-treatments selectively remove excess insulating PSS, induce conformational changes to increase charge carrier mobility, and adjust the oxidation level to enhance the Seebeck coefficient. The resulting fibers are used to fabricate flexible thermoelectric devices that demonstrate an output power density of (60.18 ± 2.79) nW cm⁻² at a temperature difference of 10 K, showcasing their superior performance and potential for practical applications in wearable energy harvesting systems. The study provides valuable insights into the development of high-performance organic thermoelectric materials by modulating polymer chains.This study presents a novel approach to enhance the thermoelectric performance of flexible PEDOT:PSS fibers through a triple post-treatment process involving concentrated sulfuric acid (H₂SO₄), sodium borohydride (NaBH₄), and 1-ethyl-3-methylimidazolium dichloroacetate (EMIM:DCA). The optimized fibers exhibit a high power factor of (55.4 ± 1.8) μW m⁻¹ K⁻² at 25 °C, significantly improving upon the original PEDOT:PSS properties. The post-treatments selectively remove excess insulating PSS, induce conformational changes to increase charge carrier mobility, and adjust the oxidation level to enhance the Seebeck coefficient. The resulting fibers are used to fabricate flexible thermoelectric devices that demonstrate an output power density of (60.18 ± 2.79) nW cm⁻² at a temperature difference of 10 K, showcasing their superior performance and potential for practical applications in wearable energy harvesting systems. The study provides valuable insights into the development of high-performance organic thermoelectric materials by modulating polymer chains.