Muscadines are berries of Vitis rotundifolia, a grape native to SE USA. Muscadine skins and seeds are sold as nutraceutical products because of their high antioxidant activity, anti-inflammatory and anti-cancer phytochemical profiles. Hyperglycemia leads to both induction and activation of aldose reductase (AR), the initial rate-limiting enzyme of the polyol pathway (conversion of glucose to sorbitol to fructose). Activation of the polyol pathway contributes to Advanced Glycation Endproduct (AGE) formation in organs with AR activity including lens of the eye, kidney, heart, nerves and liver. This pathway is implicated in diabetic cataract formation and neuropathies. Because the pharmacognosy of muscadine skins revealed many compounds with anti-AR activity, we tested the ability of muscadine skin and seed extracts to inhibit human recombinant AR (HRAR) in vitro. The results indicated that extracts of muscadine skins and seeds inhibited AR activity at low concentrations. Nutraceutical products made from muscadine skins and seeds may prove useful in inhibiting AGE formation via inhibition of the polyol pathway.