Unhealthy dietary pattern-induced type 2 diabetes mellitus poses a great threat to human health all over the world. Accumulating evidence has revealed that the pathophysiology of type 2 diabetes mellitus is closely associated with the dysregulation of glucose metabolism and energy metabolism, serious oxidative stress, prolonged endoplasmic reticulum stress, metabolic inflammation and intestinal microbial dysbiosis. Most important of all, insulin resistance and insulin deficiency are two key factors inducing type 2 diabetes mellitus. Nowadays, natural polysaccharides have gained increasing attention owing to their numerous health-promoting functions, such as hypoglycemic, energy-regulating, antioxidant, anti-inflammatory and prebiotic activities. Therefore, natural polysaccharides have been used to alleviate diet-induced type 2 diabetes mellitus. Specifically, this review comprehensively summarizes the underlying hypoglycemic mechanisms of natural polysaccharides and provides a theoretical basis for the development of functional foods. For the first time, this review elucidates hypoglycemic mechanisms of natural polysaccharides from the perspectives of their regulatory effects on glucose metabolism, insulin resistance and mitochondrial dysfunction.