The treatment of sewage generates a significant volume of activated sludge, requiring efficient volume reduction methods. Extracellular polymeric substance (EPS) in the sludge plays a crucial role in affecting dewatering performance. Traditional coagulation pretreatment struggles to effectively destroy EPS and release bound water. In this study, activated sludge from a municipal sewage treatment plant in Xianlin, Nanjing, was preoxidized with potassium ferrate (K2FeO4), and then a cationically modified lignin (LN-CD) as a coagulant to condition the oxidized sludge. We systematically investigated the dewatering performance and the synergistic mechanisms of combining K2FeO4 preoxidation and LN-CD coagulation. Our findings show that K2FeO4 preoxidation, combined with LN-CD coagulation, significantly enhances the sludge conditioning effect. The dose of the oxidizer and the charge density (CD) of the coagulant are important factors affecting the dewatering performance. Employing an optical dose of K2FeO4 preoxidation followed by LN-CD1 coagulation, which has the highest CD in this series of LN-CDs, minimized the need for coagulant while maximizing dewatering efficiency. This treatment resulted in the formation of the largest, most compact sludge flocks. Analysis of the secondary structure of proteins (PNs) in different forms of EPS revealed a transition from an ordered, compact arrangement to a looser structure following the combined preoxidation and coagulation process, which was conducive to deep dewatering. This effect is attributed to the disruption of EPS structure by K2FeO4 oxidation, releasing bound water and allowing the trivalent iron generated after the oxidation. LN-CD supports sludge particle aggregation through charge neutralization and bridging flocculation effects. Its rigid structure also serves as a skeleton builder, improving sludge cake and promoting compressibility and dewatering performance. In summary, K2FeO4 preoxidation combined with the LN-CD coagulation process should have a good application prospect in the sludge dewatering process. © 2024 Chinese Academy of Sciences. All rights reserved.