Abstract: Background and Objective: Cardiomyopathy is one of the life-threatening complications of doxorubicin chemotherapy. Doxorubicin is one of the chemotherapeutic agents used to treat cancer. The drug is effective against different types of cancers. However, the clinical application of the drug is limited due to its side effects on almost all tissues and organs. Cardiotoxicity is one of the life-threatening side-effects of doxorubicin. This study aimed to reduce the toxicity of the drug by supplementing the aqueous extract of Andrographis paniculata. Materials and Methods: In the present study, we used zebrafish (Danio rerio) as a model organism. Fishes were administered with Doxorubicin and supplemented with the aqueous extract to study the effect of the supplement. Results: The supplement successfully reduced Reactive Oxygen Species (ROS) by improving the activity of antioxidant enzymes such as Superoxide Dismutases (SOD), glutathione and catalase. Cellular damage induced by the drug was also reduced to a greater extent as indicated by lactate dehydrogenase assay and creatinine kinase activity. Histological sections of the heart treated with doxorubicin and A. paniculata also revealed the improvement in the micro-architecture and reduced inflammation as indicated by impaired neutrophil infiltration. Conclusion: Overall, it is apparent that A. paniculata is a cardioprotective agent against doxorubicin-induced cardiomyopathy.