Diet-heart presumption assumes that diets possessing high levels of saturated fats and cholesterol are potential risk aspects for developed hypercholesterolemia. There is a direct association between increased intake of cholesterol-rich food and increased cardiovascular diseases. Oxidation products of cholesterol might be formulated during high-cholesterol foods’ processing and storage. Cow ghee contains approximately 0.32% cholesterol, while buffalo ghee contains roughly 0.27%. About 10% of the cholesterol in milk fat is esterified, and the remaining amount exists in a free form. Several approaches were established to remove or decrease the cholesterol content in ghee. These approaches include biological, physical, and chemical processes. Biological methods comprise enzymes or microorganisms’ utilization. At the same time, physical methods involve short-path distillation, crystallization techniques, and supercritical fluid extraction using carbon dioxide. The chemical methods include solid-liquid extraction with adsorbents, for instance, coated porous glass, activated charcoal, plastics, or ceramics and complex mixtures with β-cyclodextrin or with an aqueous solution of bile salts and one or numerous glyceryl esters. The use of β-cyclodextrin has achieved satisfactory results. About 95% of cholesterol could be removed from ghee according to the method applied. This chapter introduces the different methods used to prepare low-cholesterol ghee and its properties.