Abstract Background: Over the past two decades, a striking increase in the number of people with the metabolic syndrome world-wide has taken place. This increase is associated with the global epidemic of obesity and diabetes. With the elevated risk not only of diabetes but also of cardiovascular disease from the metabolic syndrome, there is urgent need for strategies to prevent the emerging global epidemic. The metabolic syndrome is a master of disguise since it can present in various ways according to the different components that constitute the syndrome. Aim of Study: This study was to estimate the fasting plasma levels of PYY and ghrelin in lean versus metabolic syndrome overweighed patients. Patients and Methods: This case-control study included 20 lean (normal weight) healthy control subjects and 80 MetS subjects 20 with (abdominal obesity, high blood pressure, high blood sugar), 20 with (abdominal obesity, high blood sugar high serum triglycerides), 20 [abdominal obesity, high blood sugar low high-density lipoprotein (HDL) levels] and 20 with (high blood pressure, abdominal obesity, high serum triglycerides) the age range of the participants was 20-50 years and the participants' anthropometric characteristics were measured. Results: Total cholesterol (TC) and triglycerides (TG), Insulin, HbA1C and HOMA-IR in patients with MetS were significantly higher, while HDL-C, Ghrelin and PYY were significantly lower in MetS patients. Conclusion: The current study revealed the possible role of several GI-hormones in the pathogenesis of obesity-associated diseases and MetS. Additional works are needed to elucidate the possible underlying mechanisms and clarify several controversies in this issue.