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Background: Diabetes mellitus (DM) is a complex and prevalent metabolic disorder worldwide. Strong evidence has emerged that DM is a risk factor for the accelerated rate of cognitive decline and the development of dementia. Though traditional pharmaceutical agents are efficient for the management of DM and DM-related cognitive decrement, long-term use of these drugs are along with undesired side effects. Therefore, tremendous studies have focused on the therapeutic benefits of natural compounds at present. Ample evidence exists to prove that polyphenols are capable to modulate diabetic neuropathy with minimal toxicity and adverse effects., Purpose: To describe the benefits and mechanisms of polyphenols on DM-induced cognitive dysfunction. In this review, we introduce an updated overview of associations between DM and cognitive dysfunction. The risk factors as well as pathological and molecular mechanisms of DM-induced cognitive dysfunction are summarized. More importantly, many active polyphenols that possess preventive and therapeutic effects on DM-induced cognitive dysfunction and the potential signaling pathways involved in the action are highlighted., Conclusions: The therapeutic effects of polyphenols on DM-related cognitive dysfunction pave a novel way for the management of diabetic encephalopathy.