Oxidative stress is a key contributor to the onset and progression of diabetes and its complications. It leads to insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction. Experimental and clinical data show an inverse relationship between insulin sensitivity and reactive oxygen species (ROS) levels. Oxidative stress can arise from various sources, including disease states and lifestyle changes. It activates stress pathways involving serine/threonine kinases, which negatively affect insulin signaling. More research is needed to identify the mechanisms of insulin resistance in both type 1 and non-diabetic individuals. Controlling hyperglycemia and calorie intake can reduce oxidative stress. This review outlines mechanisms leading to oxidative stress and discusses interventions that may reduce insulin resistance and diabetes risk. Insulin is a key hormone regulating glucose homeostasis. It is secreted by pancreatic β-cells and activates signaling pathways, including the PI3K and MAPK pathways, which are crucial for glucose uptake and cellular functions. Insulin signaling is disrupted by oxidative stress, which can impair insulin receptor function and downstream signaling. ROS and the cellular redox state influence various biological processes, including phosphorylation and cell cycle regulation. Oxidative stress can disrupt redox balance, leading to cellular damage and disease progression. Hyperglycemia contributes to oxidative stress through mechanisms such as increased polyol pathway activity, advanced glycation end-products (AGEs), and activation of protein kinase C. AGEs can signal through the RAGE receptor, leading to ROS production and activation of NF-κB, which promotes inflammation and disease. Hyperglycemia also activates the DAG-PKC pathway, which can increase ROS production and impair insulin signaling. Mitochondrial dysfunction is a major contributor to oxidative stress and insulin resistance, as it affects energy production and ROS generation. Oxidative stress influences insulin signaling by impairing key components such as IRS and IR, leading to insulin resistance. Chronic oxidative stress activates stress pathways like NF-κB, JNK/SAPK, and p38 MAPK, which negatively affect insulin signaling. Mitochondrial dysfunction further exacerbates oxidative stress and insulin resistance by reducing ATP production and increasing ROS levels. Ketosis, often seen in type 1 diabetes, can increase oxidative stress and insulin resistance. Insulin sensitivity is also affected by nutrient availability and sleep restriction, which can increase inflammation and oxidative stress. Calorie restriction improves insulin sensitivity and mitochondrial function, suggesting it as a potential therapeutic approach. PTEN, a negative regulator of the PI3K/Akt pathway, influences insulin sensitivity and diabetes risk. Sleep restriction is a novel risk factor for insulin resistance and type 2 diabetes, linked to increased inflammation and oxidative stress. Antioxidant therapy may help reduce oxidative stress, but its effectiveness varies among individuals. In conclusion, oxidative stress plays a central role in the development of diabetes and its complications. Understanding the mechanisms of oxidative stress and its impact on insulin signaling is crucial for developing effective interventions toOxidative stress is a key contributor to the onset and progression of diabetes and its complications. It leads to insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction. Experimental and clinical data show an inverse relationship between insulin sensitivity and reactive oxygen species (ROS) levels. Oxidative stress can arise from various sources, including disease states and lifestyle changes. It activates stress pathways involving serine/threonine kinases, which negatively affect insulin signaling. More research is needed to identify the mechanisms of insulin resistance in both type 1 and non-diabetic individuals. Controlling hyperglycemia and calorie intake can reduce oxidative stress. This review outlines mechanisms leading to oxidative stress and discusses interventions that may reduce insulin resistance and diabetes risk. Insulin is a key hormone regulating glucose homeostasis. It is secreted by pancreatic β-cells and activates signaling pathways, including the PI3K and MAPK pathways, which are crucial for glucose uptake and cellular functions. Insulin signaling is disrupted by oxidative stress, which can impair insulin receptor function and downstream signaling. ROS and the cellular redox state influence various biological processes, including phosphorylation and cell cycle regulation. Oxidative stress can disrupt redox balance, leading to cellular damage and disease progression. Hyperglycemia contributes to oxidative stress through mechanisms such as increased polyol pathway activity, advanced glycation end-products (AGEs), and activation of protein kinase C. AGEs can signal through the RAGE receptor, leading to ROS production and activation of NF-κB, which promotes inflammation and disease. Hyperglycemia also activates the DAG-PKC pathway, which can increase ROS production and impair insulin signaling. Mitochondrial dysfunction is a major contributor to oxidative stress and insulin resistance, as it affects energy production and ROS generation. Oxidative stress influences insulin signaling by impairing key components such as IRS and IR, leading to insulin resistance. Chronic oxidative stress activates stress pathways like NF-κB, JNK/SAPK, and p38 MAPK, which negatively affect insulin signaling. Mitochondrial dysfunction further exacerbates oxidative stress and insulin resistance by reducing ATP production and increasing ROS levels. Ketosis, often seen in type 1 diabetes, can increase oxidative stress and insulin resistance. Insulin sensitivity is also affected by nutrient availability and sleep restriction, which can increase inflammation and oxidative stress. Calorie restriction improves insulin sensitivity and mitochondrial function, suggesting it as a potential therapeutic approach. PTEN, a negative regulator of the PI3K/Akt pathway, influences insulin sensitivity and diabetes risk. Sleep restriction is a novel risk factor for insulin resistance and type 2 diabetes, linked to increased inflammation and oxidative stress. Antioxidant therapy may help reduce oxidative stress, but its effectiveness varies among individuals. In conclusion, oxidative stress plays a central role in the development of diabetes and its complications. Understanding the mechanisms of oxidative stress and its impact on insulin signaling is crucial for developing effective interventions to