Synthesizing new heterocyclic steroids using some chemical strategies could be predictable to have promising efficiency against mercuric chloride-induced acute renal failure. Analytical and spectral data affirmed the structure of the unprecedented heterocyclic steroids. To assess their biological activities for 30 days, Group1: Healthy animals. Group2: Acute kidney injury were intraperitoneally injected with HgCl2 (5 mg/kg b.wt), Group3: divided into five subgroups were given one of the tested compounds (5. 6, 9 and 4 respectively) (50 mg/kg b.wt), Group4: Subjected to HgCl2 and divided into five subgroups and simultaneously treated with one of the tested compounds (5. 6, 9 and 4 respectively) (50 mg/kg b.wt.), Group5: Administered HgCl2 and treated orally at the same time with losartan in a dose of (30 mg/kg). At the end of the experimental period, synthesized compounds significantly prevented increased serum levels of creatinine, urea, renal lipid peroxidation, NO levels, decreasing serum AST, ALT, ALP, TNF-α, and IL-1 β levels and lipid profile concentration. and showed a significant increase in HDL and CAT levels. They moreover, upregulated levels of Nephrin-2 and KIM-1 Genes Expression. Histopathological results supported our biochemical findings. Noteworthy, compounds 6 and 9 in particular, have more antioxidant and anti-inflammatory activities than compounds 4 and 5 and play a salutary role against HgCl2 toxicity