Neurodegenerative disorders (NDs) refer to a diverse group of diseases characterized by the progressive loss of neurons, which leads to severe deficits in memory, cognition, behavior, sensory, and motor functions. The increasing prevalence of NDs imposes a significant burden on healthcare systems and has driven extensive research into the biological mechanisms underlying these conditions. Recent evidence highlights the critical role of the exposome—the sum of all environmental and lifestyle exposures experienced throughout life—in shaping ND risk. These exposures primarily exert their effects through epigenetic mechanisms rather than direct genetic alterations. Among epigenetic mechanisms, DNA methylation—the covalent addition of methyl groups to DNA bases—has garnered significant attention. This modification is highly sensitive to external factors, including diet, physical activity, airborne pollutants, pesticides, and viral infections, and is implicated in the onset and progression of NDs. This chapter provides an overview of the current knowledge linking the exposome, DNA methylation changes, and NDs. First, it outlines epidemiological trends and the main biological alterations, or “hallmarks,” of NDs, with a focus on the role of DNA methylation in modulating disease risk. Next, it examines the influence of various environmental and lifestyle factors on ND pathogenesis through DNA methylation changes, integrating findings from population studies and experimental models. By synthesizing existing research and identifying gaps in the field, this chapter aims to advance understanding of how exposome-driven epigenetic changes contribute to NDs. It also highlights opportunities for leveraging these insights to develop innovative diagnostic tools and therapeutic strategies.