Skeletal muscle is the largest organ in the body and constitutes almost 40% of body mass. It
is also the primary site of insulin-mediated glucose uptake, and skeletal muscle insulin resistance, that
is, diminished response to insulin, is characteristic of Type 2 diabetes (T2DM). One of the foremost
reasons posited to explain the etiology of T2DM involves the modification of proteins by dicarbonyl
stress due to an unbalanced metabolism and accumulations of dicarbonyl metabolites. The elevated
concentration of dicarbonyl metabolites (i.e., glyoxal, methylglyoxal, 3-deoxyglucosone) leads to DNA
and protein modifications, causing cell/tissue dysfunctions in several metabolic diseases such as T2DM
and other age-associated diseases. In this review, we recapitulated reported effects of dicarbonyl stress
on skeletal muscle and associated extracellular proteins with emphasis on the impact of T2DM on
skeletal muscle and provided a brief introduction to the prevention/inhibition of dicarbonyl stress.