〔Abstract〕 Objective To investigate the effect of natural product isoliquiritigenin(ILTG) on the sleep of C57 mice and the possible effects of brain areas. Methods The control group C57 BL/6 J background mice were fed with saline for 7 days, and the administration group C57 BL/6 J background mice were fed with isoliquiritigenin for 7 days(32.4 mg/kg). The mice's sleep-wakefulness processes were recorded and analyzed by electroencephalogrphy(EEG), electromyogram(EMG) and software; The water maze experiment was used to investigate whether ILTG damaged the memory ability of mice; c-fos staining was performed on the whole brain to find which regions the drugs acted on. Results(1) On the 7 th day of intragastric administration, the total amount of sleep in the administration group increased compared to the control group, non-rapid eye movement sleep(NREM) increased, there was no significant difference in REM sleep; sleep latency was shortened, and brain increased energy spectrum;(2) In the experiment of water maze, there was no significant difference in the time to find the plateau area(quadrant 5) between the control group and the drug group, and there was no significant difference in the residence time in the plateau area;(3) The c-fos staining showed that the brain regions activated by ILTG were ventrolateral preoptic area(VLPO), ventromedial preoptic nucleus(VMPO), and lower fornix(SFO). Conclusion ILTG can increase the amount of NREM sleep in C57 mice and increase the power spectrum of brain waves during NREM. The brain regions activated by ILTG's sleep-promoting effects are VLPO, VMPO, and SFO brain regions. Moreover, isoliquiritigenin has no neurotoxicity and will not damage the cognition and memory of mice.