Acute myocardial infarction (MI), a serious manifestation of ischemic heart disease, remains the culprit for mortality among coronary heart disease patients. Astaxanthin has demonstrated the ability to alleviate inflammation-induced myocardial damage while maintaining a balance between oxidants and antioxidants. This study investigates the cardioprotective potential of astaxanthin (ASX), particularly when encapsulated in nanostructured lipid carriers (NLCs), in isoprenaline (ISO)-induced myocardial infarction in rats. The study involved 48 rats separated into 6 groups. ASX and Nano-ASX (5 mg/kg) were administrated orally for 21 days before MI induction (isoprenaline, 85 mg/kg, subcutaneously). Blood and cardiac tissue samples were taken 24 h following the last isoprenaline injection for biochemical and histopathological investigation. The findings reveal that nano-formulated ASX significantly reduces oxidative stress and cardiac injury markers, including CK-MB, Troponin-I, and LDH. Additionally, it enhances antioxidant enzyme activities (GSH, GPx, and GSH-RD) and decreases inflammatory markers (COX-2 and VEGF). The study further demonstrates that nano-ASX stimulates autophagy by upregulating critical genes such as Beclin-1, ULK1, and LC3B, which are vital for cardiac protection and repair. Histological analysis confirms these biochemical outcomes, showing reduced myocardial damage and inflammation in the nano-ASX-treated groups. This study concludes the potential of ASX nano-formulations as an advanced therapeutic approach for myocardial infarction, leveraging improved bioavailability and targeting oxidative stress, inflammation, and autophagic mechanisms.