Background: Doxorubicin is a first-line drug used in cancer chemotherapy, but its severe myocardial toxicity limits its widespread use. Indole derivatives, a large class of substances widely found in natural plants and metabolic products, exhibit a variety of biological effects. Summary: Previous studies have shown that indole compounds can protect against doxorubicin-induced myocardial damage through multiple mechanisms, including antioxidant activity, mitochondrial protection, anti-inflammatory effects, ferroptosis inhibition, apoptosis suppression, and endoplasmic reticulum stress attenuation. Understanding the pathogenesis of doxorubicin-induced cardiomyopathy and the molecular mechanisms by which indole compounds protect the myocardium is crucial for the development of novel drug molecules based on indole compounds in the future. Key Messages: Focusing on the molecular characteristics of indole derivatives, investigating their pharmacodynamics and safety, and developing safe and effective antagonistic molecules to counteract doxorubicin toxicity, holds great potential, and significance.