In order to develop silk peptide (SP) preparations possessing cognition-enhancing effect, several candidates were screened through in vitro assays, and their effectiveness was investigated in facilitated brain aging model rats. Incubation of brain acetyl-cholinesterase with SP-PN (1-1,000 ${mu}g/ml$) led to inhibition of the enzyme activity up to 35%, in contrast to a negligible effect of SP-NN. The expression of choline acetyltransferase (ChAT) mRNA of neural stem cells expressing ChAT gene (F3.ChAT) was increased by 24-hour treatment with 10 and 100 ${mu}g/ml$ SP-NN (1.35 and 2.20 folds) and SP-PN (2.40 and 1.34 folds). Four-week subcutaneous injections with D-galactose (150 mg/kg) increased activated hippocampal astrocytes to 1.7 folds (a marker of brain injury and aging), decreased acetylcholine concentration in cerebrospinal fluid by 45-50%, and thereby impaired learning and memory function in passive avoidance and water-maze performances. Oral treatment with SP preparations (50 or 300 mg/kg) for 5 weeks from 1 week prior to D-galactose injection exerted recovering activities on acetylcholine depletion and brain injury/aging as well as cognitive deficit induced by D-galactose. The results indicate that SP preparations restore cognitive functions of facilitated brain aging model rats by increasing the release of acetylcholine, in addition to neuroprotective activity.