Introduction and objectives: The current study evaluates the effect of chelidonic acid doxorubicin-induced cardiac toxicity. Chelidonic acid (CA) is a natural pyran-skeleton heterocyclic compound found in rhizomes of the perennial plant, celandine (Chelidonium majus). Methods: Wistar rats were given an intraperitoneal injection of doxorubicin (1.25 mg/kg, cumulative dose of 20 mg/kg) four times per week for a duration of four weeks to induce cardiotoxicity. CA treatment (10, 20, and 40 mg/kg orally for four weeks) was started together with doxorubicin. Results: CA treatment reduced myocardial damage and improved cardiac dysfunction doxorubicin-treated rats. It improved blood pressure, restored ST wave height and normalized the QTc interval compared to the rats treated only with doxorubicin. Administration of CA four weeks reduced left ventricular end-diastolic pressure. Moreover, CA treatment decreased the level of cardiac markers such as creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and cardiac troponin-T. Masson's trichrome, hematoxylin, and eosin staining of heart tissue revealed that CA attenuated the deleterious effects of doxorubicin and prevented further damage and fibrosis in rats. Conclusion: The study findings confirm that CA treatment can protect the myocardium against doxorubicin-induced cardiotoxicity. (c) 2024 Sociedade Portuguesa de Cardiologia. Published by Elsevier Espana, S.L.U. This is open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).