Cardiovascular diseases (CVD),are the most significant cause of death in all age groups throughout the world. It is the major cause of death in most of the developed and developing countries. Coronary heart disease, congestive heart failure, high blood pressure, stroke, myocardial infarction are the major cardiovascular complications. Lagenaria siceraria (Molina), also known as Bottle gourd, is a member of Cucurbitaceae family. Lagenaria siceraria is broadly cultivated in tropical countries like India, Japan, Egypt, Thailand and most of the part of the world as a vegetable crop. Fruits of the plant have been reported to have potential beneficial effects in Ayurveda and other folk medicines. The fruit is traditionally used for its cardioprotective, cardiotonic, general tonic, diuretic, aphrodisiac and antidote activities. The edible portion of the fruits is a trustworthy source of certain phytoconstituents-like ascorbic acid, β-carotene, vitamin-B complex, choline, minerals, amino acids, triterepenoidcucurbitacins B, D, G, H, 22-deoxy cucurbitacin, β-glycosidedaseelasterase, sterols, triterpenes, flavonoids and carbohydrates. Modern pharmacological studies have shown that Lagenaria siceraria fruit possesses various cardioprotective properties. Chloroform and alcoholic extract of Lagenaria siceraria showed antihyperlipidemic potential in triton induced hyperlipidemia in rats. The fruit showed significant cardioprotective effects in Doxorubicin and Isoproterenol induced cardiotoxicity in rats. The fruit is reported to possess good antioxidant activity in vitro as well as in vivo. The present chapter is focused on in-depth scientific studies that have been carried out on cardioprotective potential of Lagenaria siceraria.