Over the recent years, numerous research efforts have been focused toward xanthones, a class of heterocyclic compounds characterized by a three-ring core structure and a diverse range of biological activities. Despite extensive studies, no xanthone-based molecule has successfully progressed through clinical trials to reach pharmaceutical applications. Xanthones belong to the class of secondary metabolites that exist naturally, found in various plant species, and their structural diversity has been further expanded through synthetic modifications to enhance their pharmacological efficacy. This review provides a comprehensive description of the therapeutic potential of xanthone derivatives within the scope of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and neuroinflammation. Existing literature has been rigorously examined to highlight the pharmacological relevance of xanthones in these disorders. Additionally, the pathophysiological aspects of each disease are discussed in detail to establish a mechanistic understanding of how xanthone derivatives may exert neuroprotective effects. Furthermore, the SAR of xanthones is explored to elucidate key molecular features responsible for their bioactivity, providing insights into rational drug design. By synthesizing and critically analyzing the existing research, this review is focused in highlighting the therapeutic relevance of xanthones in neurodegenerative diseases and their potential as lead candidates for further drug development.