To elucidate the regulatory effects of policosanol from rice bran (PS) on lipid metabolism, a systematic investigation was conducted through cell and animal experiments. A high-fat model was established in the human normal hepatocyte cell line (L02 cells) by treatment with oleic acid and palmitic acid, while a high-fat and high-cholesterol model was established in male SD rats with a high-fat and high-cholesterol (HFC) diet. Different doses of PS were administered, and lipid metabolism-related parameters were measured. The results showed that intracellular triglyceride (TG) and total cholesterol (TC) levels, as well as lipid accumulation, significantly decreased in L02 cells by PS treatment. In the HFC rat model, administration of 8 mg•kg-1 PS significantly reduced body weight (by 14.25%) and fasting blood glucose levels, while improving glucose tolerance. A marked decrease was observed in subcutaneous/abdominal/brown adipose tissue and liver weight. Serum TG and TC levels decreased by 67.57% and 68.24%, respectively, with corresponding decreases of 32.93% and 21.43% in liver TG and TC content. Furthermore, serum high-density lipoprotein cholesterol increased by 59.57%, whereas serum low-density lipoprotein cholesterol decreased by 73.39%. Additionally, liver superoxide dismutase activity was significantly enhanced. In conclusion, PS improved lipid accumulation, reduced body weight, lowered blood glucose levels, regulated blood lipid levels, and protected the liver (by alleviating liver lipid accumulation and enhancing antioxidant capacity) in high-fat and high-cholesterol-induced cell and animal models, thus providing experimental evidence for its application in food and pharmaceutical fields.