<p>Water pollution caused by textile wastewater, particularly from denim manufacturing, poses a significant environmental challenge due to its high organic load and chemical complexity. This study investigates a novel one-step hydrothermally-assisted persulfate oxidation process for the treatment of highly concentrated denim scrap wastewater. To systematically optimize the process parameters—temperature, treatment time, and persulfate concentration—a Central Composite Design within the framework of Response Surface Methodology was employed. The method achieved up to 79.25% chemical oxygen demand (COD) removal under optimized conditions. Inorganic ion analysis of treated samples revealed substantial chemical transformations, including the formation of sulfate as a major by-product and reductions in fluoride, phosphate, and calcium levels, alongside the release of halide ions and ammonium from oxidized organic compounds. Besides, pH stabilization trends were observed in relation to oxidant dosing, further supporting model reliability. Statistical models for COD removal, color removal, and pH change demonstrated high predictive accuracy, with the pH model exhibiting the greatest reliability. This study demonstrates that hydrothermally-assisted persulfate treatment is an effective and sustainable alternative to conventional advanced oxidation processes, providing a simplified, catalyst-free solution that can be integrated into industrial textile wastewater treatment systems while reducing chemical usage and environmental impact.</p>