The Chinese population is aging and the trend is becoming increasingly severe. Hence, preventing and treating neurodegenerative diseases has become a main focus in the neuroscience field. However, the pathogenesis of neurodegenerative diseases is complicated, and effective control measures have not been found up to now. Nutritional therapy may be a promising strategy. Many studies had shown that ω-3 polyunsaturated fatty acids may exert a neuroprotective role by regulating the pathophysiological processes of neurodegenerative diseases. However, whether ω-3 polyunsaturated fatty acids can prevent and treat neurodegenerative diseases remains controversial. Therefore, this study aimed to review the latest mechanisms of ω-3 polyunsaturated fatty acids in regulating neurodegenerative diseases, discuss the possible causes for conflicting results in recent studies, explore the specific pharmacological effect of ω-3 polyunsaturated fatty acids, and further understand their therapeutic efficacy in neurodegenerative diseases.