Despite the high levels of polyphenolic phytochemicals in grain sorghum and its position as a major food staple, there has been a lack of research on its effects on both animal and human health and disease prevention. These phenolic compounds, mainly located in the bran fraction, result in the plant having substantial antioxidant properties. This study examined the effect of ethanol extracts of several varieties of sorghum (S. bicolor) bran on albumin glycation, a non-enzymatic process thought to be important in the pathogenesis of many diabetic complications. Sorghum brans with a high phenolic content and high antioxidant properties inhibited protein glycation, whereas sorghum brans that are low in these properties did not inhibit this process. Ethanol extracts of wheat, rice or oat bran did not inhibit protein glycation. Although one high phenolic sorghum bran variety (sumac) inhibited protein glycation by approximately 60%, it produced only a 20% decrease in methylglyoxal mediated albumin glycation. These results suggest that certain varieties of sorghum bran may affect critical biological processes that are important in diabetes and insulin resistance. These results distinguish select sorghum brans from the common food brans and suggest a nutraceutical rationale for its human consumption.