Acteoside, an important phenylethanol glycoside, is the main active component in Osmanthus fragrans flower. Our previous study found that acteoside showed high antiaging effect but its absorption rate was low. We speculated acteoside palliated aging-related cognitive impairment before being absorbed, that was intestinal homeostasis underlie the antiaging effect of acteoside. In this study, acteoside was confirmed to palliate cognitive impairment in d-galactose induced aging mice. Acteoside treatment dramatically reduced oxidative stress, alleviated intestinal inflammation, restored intestinal mucosal barrier, rebuilt gut microbiome structure and upregulated gut microbiome metabolites short-chain fatty acids (SCFAs) and amino acids (AAs). Furthermore, antibiotic treatment revealed that the antiaging ability of acteoside was abolished in microbiota depleted mice, which offered direct evidence for the essential role of gut microbiota in the attenuation of cognitive impairment of acteoside. Together, our study indicated that acteoside palliated cognitive impairment by regulating intestinal homeostasisand acteoside intake might be a promising nutritional intervention in prevention of neurodegenerative diseases.