The clinical utility of non-specific anticancer therapies, such as anthracyclines, taxanes, and alkylating agents is often limited by their cardiotoxicity profiles. These agents exert cardiac damage through multiple mechanisms, including oxidative stress, disruption of myocardial signaling pathways, and direct myocardial injury. The resulting complications, range from arrhythmias and left ventricular dysfunction to overt heart failure, posing significant risks to patients. Consequently, there is a pressing need for targeted, mechanism-based strategies to prevent or mitigate anticancer-induced cardiac damage. Currently, cardioprotective and rescue therapies remain an active and evolving area of investigation. This chapter aims to: (1) characterize the role of oxidative stress and related signaling pathways in chemotherapy-associated cardiotoxicity, and (2) explore the therapeutic potential of naturally occurring bioactive compounds and molecularly targeted interventions.