The study aimed to explore the preventive effect of Antarctic krill protein peptide(EHAK) on memory injury caused by scopolamine in mice. The mice were divided into 5 groups: Blank control group， memory damage model group， and low (31.25 mg/kg)， medium (62.5 mg/kg) and high (125 mg/kg) dose groups of EHAK. The behavioral indices， serum and biochemical indices of the mice and the protein expression levels of hippocampal nerve cells were determined， and the states of hippocampal neurons were observed. Behavioral experiments indicated that EHAK could improve the spatial learning and memory ability of mice. Regarding the oxidative stress levels and cholinergic systems， when 125 mg/kg EHAK was administered to mice， compared with the model group， the SOD activity in serum increased by(10.13 ± 1.00) U/mg prot and the MDA content in serum decreased by(1.04 ± 0.26) nmol/mg prot. The hippocampal AChE activity and MDA content declined by (0.90 ± 0.05) U/mg prot and (1.16 ± 0.01) nmol/mg prot， respectively， while the ACh content increased by (10.13 ± 1.00) μg/mg prot. These data indicated that EHAK could attenuate scopolamine-induced cognitive impairment by preventing oxidative stress and cholinergic dysfunction. The status of hippocampal neurons showed that the EHAK could effectively prevent hippocampal neuron apoptosis and uneven arrangement. In addition， EHAK could inhibit neuronal apoptosis and regulate prominent plasticity through the BCL-XL/Bax/ Caspase-3/p53/CREB/BDNF signaling pathway. Therefore， EHAK could prevent scopolamine-induced memory impairment by modulating the cholinergic system and protecting neurons in the hippocampus， which demonstrated the potential to be used as food ingredient with functional appeal.