Vascular calcification (VC) is an impact of calcium accumulation in end-stage renal diseases, normally initiated in the mitochondria. Sodium thiosulfate (STS) is effective in rescuing mitochondrial function in the neurovascular complications associated with VC, but has limitation in protecting the cardiac mitochondria. However, the STS efficacy in restoring the renal mitochondrial function has not been studied, which is the primary focus of this study. Wistar rats (n = 6/group) were administered 0.75 % adenine in the diet for 28 days to induce renal failure. STS (400 mg/kg) was given in two regimens STS_Pre (preventive: along with adenine for 28 days) and STS_Cur (curative: 29th to 49th day). Renal failure was assessed by plasma and urinary markers. The effectiveness of treatment was assessed from oxidative stress, DNA damage, mitochondrial physiology and enzymology in the renal tissue. 0.75 % adenine diet caused renal medullary swelling, tubular interstitial nephropathy and impaired renal function (creatinine, urea, uric acid and ALP), which were recovered after STS treatment. The renal failure was due to oxidative stress as measured by elevated malondialdehyde (29 %) and lowered reduced glutathione (27 %) levels. STS reduced the lipid peroxidation and significantly (p < 0.05) elevated the antioxidant enzymes. Further, it improved renal mitochondrial respiratory capacity by maintaining the hyperpolarized membrane potential and restored the complex enzyme activities. Absence of renal DNA fragmentation supports the above findings. STS protects the kidney by preserving renal mitochondria, in experimental adenine-induced vascular calcified rats. The efficacy was prominent when given after induction, i.e., in STS_Cur group.