Nandrolone-decanoate (NA), a synthetic anabolic steroid, negatively impacts cardiac function. While exercise is known to benefit cardiovascular health, its effects on individuals misusing anabolic steroids require further study. Osteopontin (OPN) and mammalian target of rapamycin (m-TOR) are crucial in inflammation-related cardiovascular diseases and can be influenced by exercise, though results are inconclusive. This study aims to examine how exercise affects NA’s cardiac adverse effects and the potential role of OPN and m-TOR. The study involved 52 male rats divided into four groups: control, exercise-only, NA-treated (15 mg/kg/day S.C for 8 W), and combined exercise and NA treatment. Researchers measured blood pressure, heart rate (HR), serum cardiac enzymes, CRP, IL-1B, IL-6, Brain Natriuretic Peptide (BNP) and conducted macro and micromorphological assessments. Additionally, immunohistochemical analysis of cardiac OPN and mTOR was performed. The NAtreated group showed significant increases in blood pressure, HR, weight, and cardiac enzymes compared to the control group. Exercise significantly improved these parameters in the combined exercise and NA treatment group, except for blood pressure. All groups exhibited an increase in cardiac weight relative to the control. The NA-treated group displayed marked hyaline degeneration and necrosis in cardiac tissues, with increased cell diameter and excess collagen deposition, which was less severe in the combined exercise (EX) and NA treatment group. NA treatment significantly elevated inflammatory mediators and the area percentage of OPN and m-TOR expression. These markers were significantly reduced in the combined exercise and NA treatment group. BNP was remarkably raised in EX+NA group compared to all other groups. Exercise mitigated NA-induced cardiac damage by reducing inflammation, possibly through the downregulation of cardiac OPN and m-TOR expression