The effect of vitamin D on cardiac dysfunction after menopause is still under investigation. Therefore, we investigated the effect of vitamin D3 on cardiac apoptotic and structural changes in ovariectomized rats. Forty adult female albino rats were divided into 4 equal groups: sham rats, sham rats treated with vitamin D3, ovariectomized rats, and ovariectomized rats treated with vitamin D3 (500 IU/kg per day for 6 weeks, orally). Body mass, blood pressure, heart rate, and whole heart mass (WHM) were measured. Serum soluble receptors of advanced glycation end products (sRAGE), C-reactive protein, malondialdehyde, and total antioxidant capacity was estimated. Cardiac sections were stained with hematoxylin–eosin and Masson’s trichrome stain. Fas and FasL apoptosis-related proteins were detected by immunohistochemistry. Vitamin D3 treatment significantly decreased ovariectomy-induced cardiac Fas and FasL apoptosis-related proteins, whole heart mass, body mass, C-reactive protein, and malondialdehyde accompanied by decreased inflammation and reduced collagen deposition between cardiac muscle fibres. However, vitamin D3 significantly increased total antioxidant capacity and sRAGE in ovariectomized and sham treated groups. Our findings suggest that vitamin D3 treatment can prevent ovariectomy-induced cardiac structural and apoptotic changes in rats via increasing sRAGE and antioxidant activity. Our results suggest that vitamin D3 has therapeutic effect against postmenopausal cardiovascular disease.