Abstract: Diabetes mellitus is a complex metabolic disease associated with impaired insulin secretion, developing insulin resistance as well as β-cell dysfunction, that leads to abnormal glucose, protein and lipid metabolism, inflammatory responses and oxidative damages. Traditional medicines suggest a wide range of remedies for the management of symptomatologies associated with chronic disorders including diabetes mellitus. The aim of the present study is to elicit the most popular traditionally used medicinal plants for diabetes and review literatures in order to scientifically evaluate their efficacy and safety in diabetes mellitus and its complications. In addition, their molecular and cellular mechanisms of action along with active phytochemical agents were highlighted. The findings demonstrated that traditional herbal remedies perform their antidiabetic potential through different cellular and molecular mechanisms, including enhancing insulin secretion, regeneration of pancreatic β-cell, improving insulin resistance, α-glucosidase enzyme inhibitory activity and anti-inflammatory effects as well as attenuating diabetes associated oxidative stress. Suppressing hepatic glucose output and enhancing glucose uptake as key contributors in antidiabetic effect of natural remedies are mediated via stimulating glycolysis, glucose oxidation and glycogenesis, along with reducing glycogen degradation and gluconeogenesis. Since traditional natural remedies are commonly used by diabetic patients, interaction between herbs and conventional antidiabetics has also been highlighted in this study. Overall, traditional herbal remedies are possible antihyperglycemic therapeutic adjuncts and potential source of new orally active agent(s) for management of diabetes; however, more well-designed clinical trials are suggested to recognize higher levels of evidence for the confirmation of their efficacy and safety.