Background: Lead (Pb) is a toxic heavy metal that causes kidney injury and oxidative tissue damage. Current drugs to treat nephrotoxicity have multiple side-effects. Therefore, the development of novel therapeutic approaches is urgently required. Purpose: We investigated the nephroprotective efficacy of flaxseed lignan secoisolariciresinol diglucoside (SDG) against lead acetate (PbAc)-induced renal toxicity in rats. Methods: The therapeutic activity of SDG was determined using a Wistar Albino rat model. Rats were administered with lead acetate (20 mg/kg b.w.) to induce nephrotoxicity and treated with SDG (10 mg/kg b.w.) or vehicle for 5 days. Biochemical parameters were measured and histopathological studies were carried out to evaluate the nephroprotective effects of SDG. Results: There were significant changes in relative kidney weight and reduced PbAc accumulation in the kidney after treatment with SDG compared to the control. SDG treatment also led to significant decreases in the levels of blood urea and creatinine and restored levels of albumin. There was also a marked improvement in the concentration of enzymes in the group treated with SDG. Histopathological examination of renal tissues confirmed that the nephritic changes due to PbAc were ameliorated by SDG treatment. Conclusion: In conclusion, our study suggests the protective role of SDG in limiting renal cytotoxicity induced by lead acetate as a model for lead toxicity.