Cognitive impairment associated with aging is a significant and growing concern, and effective therapeutic strategies are urgently needed. In this study, we evaluated the beneficial effects of plasmalogens (PLS), phosphatidylcholine (PC), and phosphatidylserine (PS) on age-associated cognitive decline. The results showed that PLS improved spatial memory performance by 44.42 % (p < 0.05) and object recognition by 80.32 % (p < 0.05) in D -galactose-induced cognitively impaired mice. In addition, PLS significantly decreased glial fibrillary acidic protein (GFAP)-positive cells in the dentate gyrus (DG) of the hippocampus (p < 0.001). PLS also alleviated neuronal damage and protected against synaptic injury . This result was verified by a 228.01 % increase in PSD-95 expression in the hippocampus (p < 0.05). PLS showed a more prominent role for the mitigation of age-related cognitive impairment compared with PC and PS. The results of this study provide a theoretical foundation for targeted lipid intervention in cognitive impairment.