Objective To investigate the effect of sodium thiosulfate (STS) on improving coronary artery calcification (CAC) burden in patients with end-stage renal disease (ESRD) on maintenance dialysis, and to analyze its impacts on walking ability and the risk of cardiovascular events, so as to provide clinical evidence for the prevention and treatment of cardiovascular complications and the improvement of motor function in ESRD dialysis patients. Methods A total of 245 ESRD patients with maintenance dialysis complicated with coronary artery calcification admitted to our hospital from January 2023 to June 2025 were enrolled. All subjects were divided into the sodium thiosulfate group (n=123) and the placebo group (n=122) by random number table method. The placebo group received routine dialysis treatment and basic intervention for cardiovascular risk; on the basis of the regimen of the placebo group, the sodium thiosulfate group was additionally treated with intravenous infusion of sodium thiosulfate. The treatment course lasted for 6 months. CAC burden, walking ability, serum calcification-related indicators and inflammatory factors were compared between the two groups before and after treatment. The incidence of cardiovascular events was recorded during the 6-month follow-up. Results Before treatment, there were no significant differences in CAC score, 6-minute walk distance (6MWD), serum calcification-related indicators and inflammatory factors between the two groups (P>0.05). After 6 months of treatment, the CAC score in the sodium thiosulfate group was significantly lower, while 6MWD was significantly longer than those in the placebo group (P<0.05). The levels of serum phosphorus, parathyroid hormone, alkaline phosphatase, tumor necrosis factor-α and C-reactive protein in the sodium thiosulfate group were markedly lower than those in the placebo group (P<0.05). The incidence of cardiovascular events in the sodium thiosulfate group was 3.25%, which was significantly lower than 9.84% in the placebo group (P<0.05). Conclusion Sodium thiosulfate can effectively reduce coronary artery calcification burden, improve walking ability, alleviate inflammatory response, and lower the risk of cardiovascular events in ESRD dialysis patients, which possesses high clinical application value.