Polyphenols are natural substances and are enriched in vegetables, fruits, grains, bark, tea, and wine. Some polyphenols have insulin-potentiating and anti-inflammatory effects, both of which are important in obesity. Dietary supplementation with polyphenolic compounds is associated with reduced diet-induced obesity and/or metabolic syndrome in animal and human studies. Insights into mechanisms that regulate food intake and satiety have led to an increased understanding of obesity but the pathogenesis underlying obesity is lacking. Food intake is subject to a complex regulation by the hypothalamus and other brain centers including the brain stem and the hippocampus. An intricate network of interacting feedback mechanisms that involve the aforementioned neural centers along with the stomach, gut, liver, thyroid, and adipose tissue in the periphery, influence the eventual outcome of food intake and satiety. Key peripheral signals, such as leptin, insulin, and ghrelin, have been linked to hypothalamic neuropeptide systems in energy regulation. This review will examine the neural centers important in food intake, the role of various neuropeptides, and the neurohormonal influence on food intake. The potential role of polyphenols in influencing the neuroregulatory factors, the neural signaling pathways and/or the peripheral feedback mechanisms that modulate food intake will also be examined.