Growing evidence support that insulin resistance may occur as a severe problem due to chronic energetic overfeeding and subsequent obesity. When an abundance of glucose and saturated fat enter the cell, impaired blood flow, hypoxia, inflammation and macrophage infiltration in obese adipose tissue may induce oxidative stress and insulin resistance. Excessive circulating saturated fatty acids ectopically accumulate in insulin-sensitive tissues and impair insulin action. In this context, excessive hepatic lipid accumulation may play a central, pathogenic role in insulin resistance. It is thought that dietary polyphenols may ameliorate obesity-related insulin resistance by attenuating inflammatory responses and oxidative stress. The most often occurring natural polyphenolic compounds are flavonoids. In this review, the possible mechanistic effect of flavonoid-rich natural products on insulin resistance-related metabolic pathways is discussed. Polyphenol intake can prevent high-fat diet-induced insulin resistance via cell surface G protein-coupled estrogen receptors by upregulating the expression of related genes, and their pathways, which are responsible for the insulin sensitivity.