Honey, a natural substance produced by honeybees, is composed of a complex mixture of carbohydrates, water, and a small amount of proteins, vitamins, minerals, and phenolic compounds. Fructose, glucose and maltose are among the various types of sugars present in honey. Used for millennia as both food and medicine, honey has been associated with improved antioxidant capacity, modulation of the immune system, antimicrobial activities, influence on lipid values (through antihypercholesterolemic effects) and regulation of glycemic responses, among other benefits. The aim of this article was to review the effects of natural honey intake on human health, with particular reference to its influence on glycemic regulation. Several studies have focused on the potential use of honey as a nutritional supplement for healthy individuals and for those with impaired glucose tolerance, diabetes, and their related comorbidities. Such investigations have found that, compared to glucose and sucrose, the consumption of honey decreases glycemic levels and blood lipids in healthy, diabetic and hyperlipidemic individuals. Moreover, long periods of honey intake seem to reduce fasting glucose levels in humans, suggesting that honey consumption influences plasma glucose regulation, mainly through a normo- or hypoglycemic effect. Therefore, honey may be proposed as a nutritional dietary supplement for healthy individuals and for those suffering from alterations in glycemic regulation.