Muscat Bailey A grape stalk is an organic waste produced in marked amounts during the vinification of grapes. Previous studies have indicated that grape stalk is rich in bioactive phenolic compounds, and exhibits antioxidant and UV‑protective activities. However, its effects on obesity and obesity‑associated disorders have not yet been investigated. The effects of grape stalk extract on improving metabolic features were examined using a high‑fat diet (HFD)‑induced obesity mouse model. Oral administration of 200 mg/kg/day grape stalk extract over 16 weeks markedly prevented HFD‑induced obesity, hepatic steatosis, diabetic symptoms and the risk of developing cardiovascular disease. Furthermore, grape stalk extract prevented oxidative stress and inflammation caused by HFD in mice. The beneficial effect may be associated with CCAAT/enhancer‑binding protein α and peroxisome‑proliferator‑activated receptor γ down-regulation in liver tissue. Collectively, the results of the present study indicated that grape stalk extract may be a potent functional food ingredient for preventing obesity, hepatic steatosis and type 2 diabetes.