The current strategies for prevention and treatment of insulin resistance and type 2 diabetes are not fully effective and frequently accompanied by many negative effects. Therefore, novel ways to prevent insulin resistance and type 2 diabetes are urgently needed. The roots of Scutellaria radix are commonly used in traditional Chinese medicines for prevention and treatment of type 2 diabetes, atherosclerosis, hypertension, hyperlipidemia, dysentery, and other respiratory disorders. Baicalin and baicalein are the major and active ingredient extracts from Scutellaria baicalensis.A comprehensive and systematic review of literature on baicalin and baicalein was carried out.Emerging evidence indicated that baicalin and baicalein possessed hepatoprotective, anti-oxidative, anti-dyslipidemic, anti-lipogenic, anti-obese, anti-inflammatory, and anti-diabetic effects, being effective for treating obesity, insulin resistance, non-alcoholic fatty liver, and dyslipidemia. Besides, baicalin and baicalein are almost non-toxic to epithelial, peripheral, and myeloid cells.The purpose of this study is to focus on the therapeutic applications and accompanying molecular mechanisms of baicalin and baicalein against hyperglycemia, insulin resistance, type 2 diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver, and trying to establish a novel anti-obese and anti-diabetic strategy.