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Epidemiological studies have implied that diabetes mellitus (DM) will become an epidemic accompany with metabolic and endocrine disorders worldwide. Most of DM patients are affected by type 2 diabetes mellitus (T2DM) with insulin resistance and insulin secretion defect. Generally, the strategies to treat T2DM are diet control, moderate exercise, hypoglycemic and lipid-lowing agents. Despite the therapeutic benefits for the treatment of T2DM, most of the drugs can produce some undesirable side effects. Considering the pathogenesis of T2DM, natural products (NPs) have become the important resources of bioactive agents for anti-T2DM drug discovery. Recently, more and more natural components have been elucidated to possess anti-T2DM properties, and many efforts have been carried out to elucidate the possible mechanisms. The aim of this paper was to overview the activities and underlying mechanisms of NPs against T2DM. Developments of anti-T2DM agents will be greatly promoted with the increasing comprehensions of NPs for their multiple regulating effects on various targets and signal pathways.