Depiction of diabetes mellitus (DM)-mediated 4-hydroxy-2-nonenal (4-HNE) affecting multiple organs systems. DM mediated hyperglycemia generates reactive oxygen species (ROS) which in turn produces 4HNE which forms adducts with multiple organs including cardiovascular, muscle, gastrointestinal, dental, renal, nervous, bone and eye and cause multiple complications as mentioned in each organ systems. ALF: acute liver failure; BMD: bone mineral density; CAD: coronary artery disease; CHC: chronic hepatitis C; CTS: carpal tunnel syndrome; CVD: cardiovascular disease; DCM: diabetic cardiomyopathy; DKD: diabetic kidney disease; DME: diabetic macular edema; DN: diabetic nephropathy; DR: diabetic retinopathy; ED: erectile dysfunction; FA: Friedreich’s ataxia; HCC: hepatocellular carcinoma; HFpEF: heart failure with preserved ejection fraction; KF: kidney failure; MD: muscular dystrophy; MMD: myotonic muscular dystrophy; NAFLD: non-alcoholic fatty liver disease; NB: neurogenic bladder; NVG: neovascular glaucoma; PVD: peripheral vascular disease; RD: retinal Detachment.