Diabetes mellitus (DM) is characterized by hyperglycemia, resulting from defects in insulin secretion, insulin action or
both. There are several factors such as hyperlipidemia and oxidative stress (OS), namely the production of reactive oxygen/nitrogen
species (ROS/RNS), that actively contribute to the development and worsening of DM. Chalcones, also termed as benzalacetophenone or benzylidene acetophenone, present a 1,3-diaryl-2-propen-1-one scaffold that has been shown to be highly promising in the
development of new antioxidant compounds. Considering the potential interest of antioxidant therapy, the present review scrutinizes
the role of the main sources of ROS/RNS production during DM. The modulatory effect of chalcones against nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, mitochondrial respiratory chain and nitric oxide synthase, is also thoroughly discussed, establishing, whenever possible, a structure-activity relationship (SAR). From the SAR analysis, it can be stated
that the presence of catechol groups, hydroxyl and methoxyl substituents in the chalcones scaffold improves their modulatory activity
against the main sources of ROS/RNS production in DM.