The toxicity of heavy metals such as mercury (Hg) in humans and animals is well documented. The kidney is the primary deposition site of inorganic-Hg and target organ of its toxicity. The present study investigated the protective efficacy of flaxseed lignan-Secoisolariciresinol diglucoside (SDG) on nephrotoxicity induced by mercuric chloride (HgCl2). Rats were intraperitoneally injected with HgCl2 (2 mg/kg/day) and renal toxicity was induced. Subcutaneous administration of rats with SDG (5 mg/kg/day) as a pre-treatment caused a significant reversal of HgCl2 induced increase in blood urea, creatinine, glutathione s-transferase and catalase (CAT). On the other hand, administration of SDG with HgCl2 restored normal levels of albumin and superoxide dismutase (SOD). Histological examination of kidneys confirmed that pre-treatment of SDG before HgCl2 administration significantly reduced its pathological effects. Thus, the results of the present investigation suggest that SDG can significantly reduce renal damage, serum and tissue biochemical profiles caused by HgCl2 induced nephrotoxicity. Hence, SDG may be recommended for clinical trials in the treatment of kidney disorders caused by exposure to Hg.