Acute poisoning may lead to life-threatening conditions that require advanced life support, such as extracorporeal membrane oxygenation (ECMO). Data about the use of ECMO in intoxications and overdose are limited to case reports and case series. This review focuses on the classification of toxic agents, mechanisms of toxicity, treatment strategies, and predictors of mortality among ECMO-supported patients. Cardiogenic shock and arrhythmias can arise from cardiovascular toxins, including β-blockers, calcium channel blockers, and tricyclic antidepressants, while severe respiratory failure can result from respiratory toxins such as opioids and paraquat. ECMO is used as a bridge to recovery, transplantation, or adjunctive therapies, and the survival rates vary widely. Mortality predictors include severe acidosis (pH< 7.1) and the need for renal replacement therapy prior to ECMO. Despite its lifesaving potential, ECMO does not treat the underlying toxicity; it only stabilizes patients during the clearance of toxin or the administration of antidotes. Nevertheless, ECMO is a valuable but underutilized tool in managing severe poisoning that offers nonspecific organ support, particularly in refractory cardiogenic shock and respiratory failure, and it provides critical time for recovery. Future research should address data gaps, including underreporting of non-survivors, to better understand ECMO’s role and outcomes in intoxication management.