In many previous studies, the preventive effects of peanut against aging and cognitive impairment have often been unclear, so to clarify the effects we first investigated effective markers for evaluating its effects in the hippocampus of senescence-accelerated mouse prone/8 (SAMP8) mice, mainly using proteomics. The effects of dietary high-oleic peanuts on the hair appearance of SAMP8, the expression of effective markers in the hippocampus, and the TBARS and amino acid contents of the hippocampus were examined. Hippocampus solute carrier family 1 (glial high-affinity glutamate transporter), calcium/calmodulin-dependent protein kinase type II, and sodium- and chloride-dependent GABA transporter, which all are considered to be closely related to glutamic acid concentration were decreased by feeding of the samples, and the GABA/glutamic acid ratio in the hippocampus was increased by feeding with the samples. The formation of glial fibrillary acidic protein and synapsin-2, which showed higher levels in the SAMP8 than in SAMR1, and the protein expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein and dihydropteridine reductase, which are considered to be related to the formation of adrenergic neuron transmitters, were reduced by the feeding of peanuts and their germ-rich fraction. Ferulic acid, as an ester and minor component in peanuts, could be partly connected to the effect of peanuts. These results indicate that high-oleic peanuts and their germ-rich fraction can protect against aging and cognitive impairment by regulating protein expression, which could be measured by the proteomics of the above hippocampus proteins of SAMP8 and the hippocampal GABA/glutamic acid ratio.