Diabetes mellitus and its complications are one of the major health challenges of our time. Currently, more than 400 million adults are affected, a number that is expected to increase to 600 million people within the next two decades. Type 2 diabetes mellitus, or non-insulin dependent diabetes mellitus, is the most common type and its initial stages are treated with oral anti-diabetics. Though anti-hyperglycemic agents with different mechanisms of action are commercially available, their adverse events and hepato-renal toxicity are pronounced. Thus, the discovery of new and safer medicines is urgently warranted. Natural drug products have always been an important source of bio actives and drugs derived from nature still account for half of today’s approved therapeutics. This Special Issue, “Anti-diabetic Drugs from Natural Resources”, is dedicated to the discovery of new anti-diabetic lead compounds from nature. Research articles and reviews dealing with novel anti-diabetic activities of natural products and/or natural sources of anti-diabetics are therefore very welcome. Additionally, the evaluation of extracts and herbal preparations used for the treatment of diabetes mellitus by modern analytical techniques will be considered.