Diabetic complications, such as nephropathy, cataracts, and retinopathy, are the main threat and primary reason for death in diabetic patients. Numerous pieces of evidence demonstrated aldose reductase (ALR2) and oxidative stress are the two most important intervention targets for the treatment of diabetic complications. We designed a new type of multifunctional ALR2 inhibitor (ARI) based on the quinoxalin-2(1H)-one scaffold, which combined the inhibition of aldose reductase and direct antioxidation into an organic whole. Most of the compounds 6 showed potent ALR2 inhibition with IC