Objective To study the influence of semen platycladi saponins on oxidative stress response of hippocampus of rat model of Alzheimer’s disease (AD), and to explore the neuroprotective mechanism of semen platycladi saponins (SPS) on AD model rats. Methods Sixty SPF 24-week old female Wistar rats were divided into three groups:the normal control group, AD model group, and SPS intervention group. The rats of AD model group and SPS group were injected with Aβ1-42in bilateral hippocampi to produce AD animal models. After the successful establishment of AD model, the AD model group and the normal control group received 5 mL saline sodium with carboxymethyl cellulose (500 mg/kg) orally, daily for 30 days. The SPS group received orally 5 mL normal saline with 300 mg/kg SPS daily for 30 days. The learning and memory function of the rats were assessed by Morris water maze test, and the levels of MAD, SOD and GSH in the hippocampal tissues of model rats were detected with biochemistry. The expressions of Bcl-2, survivin, Fas, Bax, caspase-3 proteins and mRNA in the hippocampi of AD model rats were detected by western blotting. Results Compared with the control group and SPS group, the rats in AD model group displayed a longer search time and shorter percentage of search distance (P＜ 0. 01). There was a longer search time and lower percentage of search distance of the SPS groups than the control group (P＜ 0. 01). The positioning experiment showed that rats in the control group learned to find the platform within 2. 1 days, indicating that the latency was rapidly decreased. MDA in the SPS intervention group was significantly decreased than in the AD model group (P＜ 0. 01), but increased than the normal control group (P＜0. 01). The expressions of SOD and GSH were significantly increased in the SPS group than the model group (P＜ 0. 01). The expressions of Bcl-2 and survivin were significantly increased in the SPS group than the model group (P＜ 0. 01), but lower than the normal control group (P＜ 0. 05). The expressions of Fas, Bax and caspase-3 were decreased in the SPS intervention group (P ＜ 0. 01 ), but increased than the normal control group (P ＜ 0. 05 ). Conclusions Semen platycladi saponins can protect the neurons and improve the cognition function of AD model rats by inhibiting oxidative stress response and enhancing the antioxidant mechanism in the hypocampus.