Ethnopharmacological relevance: Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate.Aim of the study: Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored.Materials and methods: ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). Results: Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex. Conclusion: Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia.