Onion (Allium cepa L.) is one of the richest sources of flavonoids in human diet. Onion peel contains over 20 times more quercetin than onion flesh. In this study, we studied the effects of onion peel water extract (OPE) on the blood lipid profiles in mice. The onion peel extracts was extracted with hot water. The experimental groups were divided with 3 groups (n = 6) of ICR male mice: normal diet + distilled water (NC), high-fat diet + distilled water (HF), high-fat diet + onion peel water extract 20 mg/kg (OPE-20). The oral administration was conducted daily. The experimental period was 7 weeks. Onion peel water extract showed higher concentration of polyphenol gallic acid and anti-oxidant trolox equivalent than the ethanol extract. The body weight gain and food efficiency ratio was significantly lower in the OPE-20 group as compared with HF group (p < 0.05). The epididymal fat and retroperitoneal fat showed significantly lower weights and sizes in the OPE-20 group as compared with HF group (p < 0.05). The serum levels of total cholesterol, LDL cholesterol and triglyceride were significantly lower in the OPE-20 group as compared with HF group (p < 0.05). The OPE-20 group showed higher HDL cholesterol concentration than HF group (p < 0.05). Atherogenic index was ignificantly lower in as compared with HF group (p < 0.05). The serum levels of glucose, GOT and GPT were significantly lower in the OPE-20 group as compared with HF group (p < 0.05). In these results, we suggests that onion peel water extracts supplementation can reduces the serum lipid components and improves the lipid metabolism in hyperlipidemic mice induced with a high-fat diet.