Cognitive dysfunction (CD) is manifested as forgetfulness and memory loss, accompanied by language, mental, motor dysfunctions and etc. Rhizoma Polygonati (RP) is a traditional Chinese medicine for both medicinal and edible uses in China, which have the functions of improving learning and memory abilities, but neuroprotection of Rhizoma Polygonati (RP) on Mice with Cognitive Dysfunction is unclear. In present study, the ability of processed RP improving CD mice induced by D-galactose (D-gal) was investigated. The results showed that gavage administration of RP could significantly increase the new object recognition index and improve behavioral ability of CD mice through Morris water maze and step-down tests. RP recovered the impaired cells in the hippocampus caused by D-gal. RP enhanced the anti-oxidative activity by increasing the T-AOC and decreasing the MDA content, and significantly inhibited the inflammation in the nervous system by declining the contents of TNF-α and IL-6 in the hippo-campus of mice. These results indicated that RP had a significant protective effect on D-gal induced cognitive dysfunction mice.