Oxidative stress plays a critical role in numerous pathological processes. Under these stress conditions, the free radical-catalyzed lipid peroxidation generates in vivo a large number of key products that are involved in many physiological and pathophysiological processes. Among these products are neuroprostanes, which arise from the peroxidation of docosahexaenoic acid (DHA), and isoprostanes, resulting from arachidonic acid (AA) and eicosapentaenoic acid (EPA) through the same peroxidation process. These non-enzymatic oxygenated metabolites newly appointed NEO-PUFAs have gained recognition as reliable markers of oxidative stress in neurogenerative and cardiovascular diseases. Moreover, some of them display a wide range of biological activities. The ability to detect and measure these metabolites offers precious insights into the mechanisms of oxidative damage and holds potential therapeutic implications for various health conditions, including neurodegenerative diseases. This review focuses on the role of neuroprostanes as biomarkers for oxidative stress and related diseases, highlighting their potential applications in medical research and treatment.