Chronic or intermittent hyperglycemia is linked to the development of diabetic complications, involving oxidative stress, advanced glycation end products (AGEs), and cellular death. Reactive oxygen species (ROS) play a central role in these complications through signaling pathways such as diacylglycerol (DAG), protein kinase C (PKC), and NADPH-oxidase. These pathways lead to inflammation, cytokine secretion, and cell death, contributing to complications like retinopathy, nephropathy, and neuropathy. Hyperglycemia activates a "dangerous metabolic route" involving DAG, PKC, and NADPH-oxidase, leading to ROS production and oxidative stress. Therapeutic targets include modulating these pathways to reduce ROS, oxidative stress, and cell death. Inhibitors of DAG, PKC, and NADPH-oxidase have been tested for their potential to control diabetic complications. Drugs like Ruboxistaurin and GKT137831 have shown promise in reducing ROS and inflammation. NADPH-oxidase inhibitors, such as rutin and GKT137831, also show potential in mitigating oxidative stress. Current research highlights the importance of targeting these pathways to manage diabetic complications, although further studies are needed to validate their efficacy and safety. The review emphasizes the need for a deeper understanding of these mechanisms to develop effective therapies for diabetes.Chronic or intermittent hyperglycemia is linked to the development of diabetic complications, involving oxidative stress, advanced glycation end products (AGEs), and cellular death. Reactive oxygen species (ROS) play a central role in these complications through signaling pathways such as diacylglycerol (DAG), protein kinase C (PKC), and NADPH-oxidase. These pathways lead to inflammation, cytokine secretion, and cell death, contributing to complications like retinopathy, nephropathy, and neuropathy. Hyperglycemia activates a "dangerous metabolic route" involving DAG, PKC, and NADPH-oxidase, leading to ROS production and oxidative stress. Therapeutic targets include modulating these pathways to reduce ROS, oxidative stress, and cell death. Inhibitors of DAG, PKC, and NADPH-oxidase have been tested for their potential to control diabetic complications. Drugs like Ruboxistaurin and GKT137831 have shown promise in reducing ROS and inflammation. NADPH-oxidase inhibitors, such as rutin and GKT137831, also show potential in mitigating oxidative stress. Current research highlights the importance of targeting these pathways to manage diabetic complications, although further studies are needed to validate their efficacy and safety. The review emphasizes the need for a deeper understanding of these mechanisms to develop effective therapies for diabetes.