Diabetic keratopathy (DK) is a significant ocular complication of diabetes mellitus (DM), affecting up to 70% of diabetic patients. It is characterized by corneal epithelial defects, reduced sensitivity, and delayed wound healing, leading to corneal opacities and potential irreversible visual loss. The primary objective of this review is to provide a comprehensive overview of the pathomechanisms underlying DK, focusing on redox signaling pathways and their role in corneal and tear film alterations. The review highlights the increased production of advanced glycation end products (AGEs) and reactive oxygen species (ROS) under hyperglycemic conditions, which contribute to oxidative stress and inflammation. Key molecular pathways, such as the NLRP3 inflammasome, NF-κB, and RAGE, are discussed, along with their involvement in corneal nerve damage and corneal epithelial cell death. Additionally, the review explores experimental findings on potential treatments targeting oxidative stress, including antioxidants, Nrf2 activators, and SIRT1 modulators. These compounds have shown promise in enhancing corneal wound healing, nerve regeneration, and improving tear film function. The review emphasizes the need for further clinical trials to validate the effectiveness and safety of these antioxidants for human use, aiming to address the multifaceted nature of diabetic corneal alterations and dry eye disease (DED).Diabetic keratopathy (DK) is a significant ocular complication of diabetes mellitus (DM), affecting up to 70% of diabetic patients. It is characterized by corneal epithelial defects, reduced sensitivity, and delayed wound healing, leading to corneal opacities and potential irreversible visual loss. The primary objective of this review is to provide a comprehensive overview of the pathomechanisms underlying DK, focusing on redox signaling pathways and their role in corneal and tear film alterations. The review highlights the increased production of advanced glycation end products (AGEs) and reactive oxygen species (ROS) under hyperglycemic conditions, which contribute to oxidative stress and inflammation. Key molecular pathways, such as the NLRP3 inflammasome, NF-κB, and RAGE, are discussed, along with their involvement in corneal nerve damage and corneal epithelial cell death. Additionally, the review explores experimental findings on potential treatments targeting oxidative stress, including antioxidants, Nrf2 activators, and SIRT1 modulators. These compounds have shown promise in enhancing corneal wound healing, nerve regeneration, and improving tear film function. The review emphasizes the need for further clinical trials to validate the effectiveness and safety of these antioxidants for human use, aiming to address the multifaceted nature of diabetic corneal alterations and dry eye disease (DED).