Objective To investigate the effect and mechanism of Mongolian medicine Heisuga-25 on Alzheimer’s disease (AD) mice. Methods Six month old SAMP8 mice were divided into model group, Heisuga-25 [360 mg/(kg.d), 90 mg/(kg.d)] treatment group, and donepezil control group[0.92 mg/(kg.d)], with 15 mice in each group. Another 15 6-month-old normal aging SAMR1 mice were selected as blank control group. The mice in the model group and blank control group were fed with normal saline, and the other groups were gavaged according to the dosage. All groups were gavaged once a day for 15 days. From Day 1 to Day 5 after administration, three mice in each group were taken and Morris water maze test was been used to detect the escape latency, times for crossing the platform and the residence time were detected. Nissl staining was used to observe the number of Nissl bodies. Western blot analysis and immunohistochemistry were used to detect the expression of microtubule associated protein 2 (MAP-2) and low molecular weight neurofilament protein (NF-L). ELISA was used to detect the contents of acetylcholine (ACh), 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) in cortex and hippocampus of mice. Results Compared with the blank control group, the escape latency was significantly prolonged, while the model group showed a decrease in the number of crossing the platform, residence time, Nissl bodies, and the protein expression of MAP-2 and NF-L. Compared with the model group, Heisuga-25 administration group exhibited an increase in the number of crossing the platform and residence time, Nissl bodies, and the protein expression of MAP-2 and NF-L, but a shortened escape latency. The effect of high-dose groupHeisuga-25 [360 mg /(kg.d)] on the above indexes was more obvious. Compared with the blank control group, the contents of ACh, NE, DA and 5-HT in hippocampus and cortex were decreased in the model group. Compared with the model group, the low-dose group, high-dose group and donepezil control group all observed an increase in the contents of ACh, NE, DA and 5-HT. Conclusion Mongolian medicine Heisuga-25 can improve learning and memory by protecting the neural function of AD model mice, which may be accounted for up-regulation of neuronal skeleton protein expression and increased content of neurotransmitters.