Fruit peels are generally considered as waste. This may not hold true for all types of fruit peels. Therefore, an attempt has been made to reveal the protective role of Citrus sinensis, Punica granatum, and Musa paradisiaca peel extracts in diet-induced atherosclerosis and thyroid dysfunction in rats. Wistar albino male rats were fed an atherogenic diet composed of 4% cholesterol, 1% cholic acid, and 0.5% 2-thiouracil (CCT) for 14 days to induce atherosclerosis and were then treated with one of the standardized doses of a peel extract (25 mg/kg of C sinensis, 200 mg/kg of P granatum, or 100 mg/kg of M paradisiaca) for 10 consecutive days. At the end of the experimental period, changes in the levels of different serum lipids, thyroid hormones, insulin, and tissue and serum lipid peroxidation were determined in rats. In addition, histologic evaluation of liver, heart, and kidney were compared between the CCT-fed rats and those that received both the CCT diet as well as the peel extracts. In rats fed the CCT diet alone, there was an increase in tissue lipid peroxidation, serum lipids, and glucose, with a parallel decrease in the levels of triiodothyronine and thyroxine, insulin, and high-density lipoprotein cholesterol. Abnormal histologic observations such as fatty liver with vacuolated hepatocytes, fatty cyst and nucleus pushed to periphery, and increased cardiomyocyte width and mild damage in renal tissues were seen in these rats. However, simultaneous treatment with C sinensis, P granatum, or M paradisiaca extract ameliorated most of the biochemical and histopathologic alterations induced by the CCT diet, suggesting the protective role of these fruit peels against diet-induced atherosclerosis and thyroid dysfunction.