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Chronic hyperglycemia is an established risk factor for the development of complications in both type 1 and type 2 diabetes, but glycemic variability has emerged as a possible independent risk factor for diabetes complications, possibly through oxidative stress. In this review, methods to access glycemic variability and oxidative stress, as well as their correlations, are discussed. Non-pharmacological and pharmacological strategies are also debated to achieve better glycemic control, not only by HbA1c target but also with reduced glycemic fluctuations, possibly minimizing the risk of diabetes complications.