<p>Uranium—an emerging pollutant that exhibits both radioactivity and heavy metal toxicity—is extensively used in nuclear fuel and military applications. Occupational and environmental exposure during its extraction, production, and utilization poses significant health risks. Consequently, developing effective countermeasures against uranium poisoning remains a critical challenge in the field of medical research. This review systematically introduces the latest experimental progress in research on drugs for treating uranium toxicity. It specifically elucidates the mechanisms and efficacy evaluations of multiple detoxification strategies, including chelating agents, nanomedicines, biosynthetic compounds, small molecules, natural medicines, and plant extracts. By analyzing innovative drug design principles and evaluating their mechanistic effects on uranium toxicity, this work provides critical insights for the future development of highly effective and low-toxicity novel therapies for uranium poisoning.</p> Graphical abstract <p></p>