Diabetes mellitus (DM) belongs to the category of socially significant diseases with epidemic rates of increases in prevalence. Diabetic nephropathy (DN) is a specific kind of kidney damage that occurs in 40% of patients with DM and is considered a serious complication of DM. Most modern methods for treatments aimed at slowing down the progression of DN have side effects and do not produce unambiguous positive results in the long term. This fact has encouraged researchers to search for additional or alternative treatment methods. Hyperglycemia has a negative effect on renal structures due to a number of factors, including the activation of the polyol and hexosamine glucose metabolism pathways, the activation of the renin–angiotensin–aldosterone and sympathetic nervous systems, the accumulation of advanced glycation end products and increases in the insulin resistance and endothelial dysfunction of tissues. The above mechanisms cause the development of oxidative stress (OS) reactions and mitochondrial dysfunction, which in turn contribute to the development and progression of DN. Modern antioxidant therapies for DN involve various phytochemicals (food antioxidants, resveratrol, curcumin, alpha-lipoic acid preparations, etc.), which are widely used not only for the treatment of diabetes but also other systemic diseases. It has also been suggested that therapeutic approaches that target the source of reactive oxygen species in DN may have certain advantages in terms of nephroprotection from OS. This review describes the significance of studies on OS biomarkers in the pathogenesis of DN and analyzes various approaches to reducing the intensity of OS in the prevention and treatment of DN.