The use of herbal or natural medicines for the treatment of various disorders has a long and extensive history. Many of these herbal medicines are finding their way onto the world market as alternatives to prescribed drugs currently available to treat various disorders/ailments. In particular, hyperlipidaemia is a major risk factor for atherosclerotic coronary vascular disease, which can culminate in mortality in diabetes mellitus. There is overwhelming evidence that patients with type 2 diabetes mellitus often have metabolic syndrome and require a multifactorial intervention including aggressive treatment of arterial hypertension and dyslipidaemia to prevent cardiovascular complications. One of the most active areas of metabolic research into potential treatments is in the role of nuclear receptors as therapeutic targets for both glucose and lipid metabolism. The purpose of this review is to highlight the recent advances made by pharmaceutical and research organizations in identifying biologically active compounds from natural plant products capable of modulating nuclear receptors such as peroxisome proliferator-activated receptors and, to a lesser extent, liver X receptor and farnesoid X receptor. The specific features presented by these receptors provide an in-depth insight into the pathogenesis of metabolic disease and thus, a means of establishing potential mechanisms of action with traditional medicine. In hindsight, the review offers valuable information for rational drug design using known active compounds of plant origin. Further research may ultimately lead to a reduction in both the chronic microvascular complications of type 2 diabetes mellitus and the risk of cardiovascular disease and metabolic syndrome with the use of traditional medicine.