Azithromycin (AZ) is an effective macrolide antibiotic that has been used in the treatment of various types of serious bacterial infections. However, the cardiovascular adverse effects associated with (AZ) have recently attracted attention.The current study aimed to evaluate the protective effect of bioactive compounds in pomegranate molasses (pm) and its peels as anti-agent cardiotoxicity induced by azithromycin in male rats. The rats were divided into two main groups. The first group (6 rats) was fed on a basal diet and served as a negative control. The second group (30 rats)  received Azithromycin (AZ) from the 14th to the 28th day to induce cardiotoxicity. The second group was divided into five subgroups. Group (1) was fed on basal diet only (and served as positive control),Group (2) was fed on a basal diet + a daily oral dose of Pomegranate molasses (2 ml /kg B.W/day), Group (3) was fed on a basal diet + a daily oral dose of Pomegranate molasses (4 ml /kg B.W/day), Group (4) was fed on a basal diet + a daily oral dose of Pomegranate peel extract (200 mg/kg), Group (5)was fed on a basal diet + a daily oral dose of Pomegranate peel extract (400 mg/kg) for 28 days. At the end of the experiment, feed intake (FI), body weight gain (BWG), feed efficiency ratio (FER), and relative heart weight were calculated. Assessment of some serum biochemical parameters, heart tissues were analyzed for antioxidant/oxidant markers and  histopathology of hearts was assessed. The results revealed that pomegranate molasses and its peels improved the biological evaluation, heart functions, antioxidant enzyme activity, and histopathology of hearts compared to the positive group. In conclusion, administering pomegranate molasses and its peel extract can lower the impacts of azithromycin on the heart.