Type 2 diabetes (T2DM) is a chronic disorder categorized by hyperglycemia due to insulin resistance of cells. T2DM can cause many micro or macrovascular complications. Metformin, a biguanides derivative, has multiple benefits except anti-hyperglycemia effect, comprising amelioration blood cholesterol levels, blood pressure and depressing vascular complications accompanied with T2DM. It is proposed that metformin act via adenosine monophosphate-activated protein kinase (AMPK) -dependent or -independent approaches. The mechanisms by which metformin regulates glycemic level in T2DM are complex. In addition to its peripheral effects on insulin resistance and glycogenesis, metformin has direct beneficial effect on the beta-cell secretion. A large part of the metabolic advantages of metformin can be related to effects on gastrointestinal glucose uptake and the interaction of metformin with numerous new objects for glucose depressing in the gastrointestinal tract, including the incretin receptors, bile salt transporters and the gut microbiota.