Objective To explore the effect of total glucosides of Cistanche deserticola on oxidative stress and cognitive function in rats with intermittent hypoxia. Methods Adult male Wistar rats (n=72) were randomly divided into three groups: a blank control group, a 5% intermittent hypoxia group (IH group) and a total glucosides of Cistanche deserticola intervention group (TGs intervention group). The 5% intermittent hypoxia rat model was simulated by using the self-made cabin of intermittent hypoxia. The rats in the IH group and the TGs intervention group were given 5% intermittent hypoxia respectively, and the rats in the TGs intervention group were treated with total glucosides of Cistanche deserticola simultaneously. Learning and memory function was tested by Morris water maze in three groups at the 2nd, 4th, 6th and 8th week respectively. The expressions of superoxide dismutase (SOD) and malondialdehyde (MDA) in hippocampus were detected by test kit. Results Compared with the blank control group, the escape latency time of the rats in the IH group and the TGs intervention group was significantly prolonged at the 2nd, 4th, 6th and 8th week respectively (P<0.05). The time to cross the target quadrant in the IH group and the TGs intervention group was gradually shortened at the 2nd, 4th, 6th and 8th week respectively (P<0.05). Compared with the IH group, the escape latency gradually shortened at the 2nd, 4th, 6th and 8th week in the TGs intervention group (P<0.05), while the time to cross the target quadrant was gradually prolonged at the 2nd, 4th, 6th and 8th week (P<0.05). The expressions of MDA in hippocampal tissue in the IH group and the TGs intervention group increased at the 2nd, 4th, 6th and 8th week (P<0.05), which were significantly higher than those in the blank control group; and the expressions of SOD at the 2nd, 4th, 6th, and 8th week were all lower than those in the blank control group(P<0.05). Compared with the IH group, the expression of MDA protein in hippocampal tissue in the TGs intervention group decreased at the 2nd, 4th, 6th and 8th week, while the expression of SOD protein at the 2nd, 4th, 6th and 8th week increased, and the differences were statistically significant (P<0.05). Conclusion The total glycosides of Cistanche deserticola can improve the learning and memory function of intermittent hypoxia rats by inhibiting oxidative stress.