This review discusses the role of mitochondrial function in diabetes and its complications, focusing on the impact of hyperglycemia and oxidative stress. Hyperglycemia, a key factor in diabetes, activates several molecular mechanisms that cause tissue damage, including increased polyol pathway flux, advanced glycation end product (AGE) formation, protein kinase C (PKC) activation, and hexosamine pathway flux. These mechanisms are linked by the overproduction of superoxide, which is a major source of reactive oxygen species (ROS) in mitochondria. Oxidative stress plays a crucial role in the development and progression of diabetes and its complications, as it impairs antioxidant defenses and leads to mitochondrial dysfunction. The review also highlights the importance of mitochondrial uncoupling proteins (UCPs) in regulating mitochondrial membrane potential and ROS production, and their potential as therapeutic targets. Additionally, it explores the relationship between mitochondrial DNA (mtDNA) mutations and diabetes, as well as the impact of mtDNA copy number changes on mitochondrial function. The review concludes by discussing new therapeutic strategies, such as targeting ROS production and enhancing mitochondrial function, and the potential of mitochondria-targeted antioxidants and pharmacological agents to combat diabetic complications.This review discusses the role of mitochondrial function in diabetes and its complications, focusing on the impact of hyperglycemia and oxidative stress. Hyperglycemia, a key factor in diabetes, activates several molecular mechanisms that cause tissue damage, including increased polyol pathway flux, advanced glycation end product (AGE) formation, protein kinase C (PKC) activation, and hexosamine pathway flux. These mechanisms are linked by the overproduction of superoxide, which is a major source of reactive oxygen species (ROS) in mitochondria. Oxidative stress plays a crucial role in the development and progression of diabetes and its complications, as it impairs antioxidant defenses and leads to mitochondrial dysfunction. The review also highlights the importance of mitochondrial uncoupling proteins (UCPs) in regulating mitochondrial membrane potential and ROS production, and their potential as therapeutic targets. Additionally, it explores the relationship between mitochondrial DNA (mtDNA) mutations and diabetes, as well as the impact of mtDNA copy number changes on mitochondrial function. The review concludes by discussing new therapeutic strategies, such as targeting ROS production and enhancing mitochondrial function, and the potential of mitochondria-targeted antioxidants and pharmacological agents to combat diabetic complications.