Betaine (N, N, N-trimethylglycine) is an amino-acid derivative exerting numerous beneficial effects on the organism. This compound is found in human and animal diets but is also endogenously generated. However, its synthesis may be insufficient to maintain or improve health. Moreover, the tissue content of betaine reduces under some pathological conditions, such as type 2 diabetes. This decrease may be, however, easily alleviated by dietary betaine supplementation. Rodent studies provided evidence that betaine effectively limits many diabetes-related disturbances. Betaine therapy improves glucose tolerance and insulin action, which is strongly associated with changes in insulin-sensitive tissues, such as skeletal muscle, adipose tissue, and liver. Betaine supplementation positively affects multiple genes, which expression is dysregulated in diabetes. AMP-activated protein kinase is thought to play a central role in the mechanism underlying the anti-diabetic betaine action. Moreover, studies with animal models of type 2 diabetes have shown that betaine exerts anti-inflammatory and anti-oxidant effects, and also alleviates endoplasmic reticulum stress. These changes contribute to improved insulin sensitivity and better blood glucose clearance. The results of animal studies encourage the exploration of the therapeutic betaine efficacy in humans with type 2 diabetes.