Objective This study aimed to investigate the effects of Aβ3-10KLH active immunization on brain aging in the SAMP8 rapid aging mouse model using oxidative stress as the entry point. Methods SAMP8 mice were immunized with the Aβ3-10KLH vaccine, and a control group was established. Behavioral changes were observed using the Morris water maze test, and hippocampal morphological changes were examined using hematoxylin and eosin staining. The proportion of senescent cells in the hippocampus was detected using SA-β-gal staining. Biochemical kits were used to measure the changes in oxidative stress injury indicators malondialdehyde (MDA) and superoxide dismutase (SOD) activities to assess oxidative stress damage in the hippocampus. Results The Aβ3-10KLH vaccine attenuated cellular aging in the hippocampi of SAMP8 mice. It also improved memory ability (P < 0.05), ameliorated hippocampal tissue morphology, decreased the proportion of senescent cells in the hippocampus (P < 0.05), lowered MDA content (P < 0.05), and upregulated SOD activity (P < 0.05) . Conclusion The Aβ3-10KLH vaccine significantly improves cognitive function in SAMP8 mice, slows down the aging of hippocampal neurons, and reduces oxidative stress damage.