To explore the function and mechanism of Rehmannia on D-galactose induced the model of learning and memory impairment in aging mice. The experimental animals were randomly divided into 5 groups, except the blank group, the other groups were treated with D-galactose (200 mg/kg) to create the model of learning and memory impairment in aging which lasted for 8 weeks, starting from the 5th week, at the same time, ginkgo biloba (0.01 g/kg), low and high doses of rehmannia (1.95 g/kg, 3.90 g/kg) were given intragastric administration, the blank group and the model group were given intragastric administration with equal volume of normal saline, which lasted for 4 weeks, and Morris water maze was used for detection from the 9th week. The structural changes of brain tissues were observed by hematoxylin-eosinstaining, the immunohistochemical was detected, the biochemical was determined, the 16SrDNA intestinal flora was detected. The results show that compared with the blank group, the incubation period of the model group is prolonged, the serum superoxide dismutase(SOD), glutathione peroxidase(GSH-Px) are decreased, Malondialdehyde(MDA) is increased, and the expression of SOD and GSH-Px in the brain tissue is decreased, MDA is increased. Compared with model group, the latency of Rehmannium group is shortened (P < 0.05), SOD and GSH-Px are increased, and MDA is decreased, SOD and GSH-Px are increased in the brain tissue, MDA is decreased(P < 0.01). At the phylum level, Firmicutes and Bacteroidetes are the main Bacteroidetes in the intestinal flora of the mice (P < 0.01). The proportion of Bacteroidetes/Firmicutes (B/F) in the two groups is reduced, the proportion of the rehmannia group is lower than the model group (P < 0.05). Compared with the blank group, the relative abundance of Proteobacteria and Epsilonbacteraeota in the model group is significantly lower down(P < 0.01). Compared with the model group, the relative abundance of Proteobacteria and Epsilonbacteraeota in the low rehmannia group is decreased (P < 0.05). At the genus level, compared with the blank group, the relative abundance of Muribaculaceaege is increased in the model group(P < 0.01), while the relative abundance of Helicobacter and Halomonas is significantly decreased (P < 0.01). Compared with the model group, the relative abundance of Lachnospiraceae-NK4A136-group in Rehmannia low group is increased (P < 0.01), and the relative abundance of Muribaculaceaege is decreased (P < 0.01). Rehmannia can improve the learning and memory ability and delay the senescence of aging mice, and its mechanism may be related to anti-oxidative stress regulating the diversity of intestinal flora.