Objective To study the effects of dammarane sapogenins (DS-1226) on sleep interruption-induced learning and memory impairment in mice. Methods 130 SPF healthy 5-6-week old male ICR mice were randomly divided into control, model, DS-1226 low dose, DS-1226 medium dose and DS-1226 high dose groups. The behavioral alterations in open field (OF), Morris water maze (MWM) and step-through (ST) tests were detected at 15 days after rotating drum-induced sleep interruption (SI). Results The total distance, movement speed, total duration of movement were increased in OF test (P<0.05, vs. the model group) after treatment. The latency of place navigation was increased from day 5 in the MWM test after 15 d sleep interruption, and the number of crossing in the target quadrant and the percent distance in target quadrant were decreased after 15 d sleep interruption (P<0.05, vs. the control group), while the latency of place navigation was decreased, and the percent distance in target quadrant and percent time in target quadrant after high dose DS-1226 oral administration (P<0.05, vs. the model group) were increased. Error times, distance in dark chamber, time in dark chamber and immobility time in dark chamber were increased in training of step through test (P<0.05, vs. the control group); while these indexes were decreased after DS-1226 oral administration (P<0.05, vs. the model group). But there was no significant difference in the step through testing course. Conclusions The results show that orally administrated DS-1226 can ameliorate SI-induced learning and memory impairment, and there is a significant dosage-effect relationship.