<p>Lead is a major environmental pollutant and a poisonous substance that induces oxidative stress. It is responsible for several serious diseases associated with its toxicity. Its presence in the environment mostly affects children, mining workers, and pregnant women. Multiple studies are underway to investigate the mechanisms of lead-induced renal damage and associated diseases. Several mechanisms contribute to lead-induced nephrotoxicity, resulting in nephron damage and eventually inducing acute kidney injury (AKI) and chronic kidney disease (CKD). Chelation therapy is currently the main approach for the treatment of lead toxicity. However, recent research is increasingly exploring the potential of naturally occurring bioactive compounds, plant-derived extracts, and nanotechnology-based strategies as alternative treatments for lead poisoning. This review focuses on the mechanistic effects of toxicity and the various categories of compounds that have a beneficial impact on lead-induced renal toxicity. Plant extracts are significant in mitigating lead intoxication. A combination of phyto-bioactive and chelating agents is used for the treatment of lead toxicity. Cerium- and selenium-derived nanoparticles are used for therapeutic purposes. Further research is required to investigate the therapeutic potential of these therapeutic interventions.</p>