Some herbal medications like berberine and ipriflavone have a potential effect on Alzheimer. We studied the effect of berberine/ipriflavone mixture on the memory deficit and cognitive dysfunction which are induced by scopolamine and causing Alzheimer-like disease. 56 male Wistar rats were randomly subdivided into seven groups; including, two control groups (one received saline and the other one received polyethylene glycol), induced group, and four different treated groups (berberine, ipriflavone, berberine/ipriflavone mixture, and donepezil). Induced group and treated groups were received 2 mg/kg scopolamine intraperitoneally, once a day for 4 weeks. Berberine or ipriflavone orally administered (50 mg/kg dissolved in 20% polyethylene glycol). Group of berberine/ipriflavone mixture was orally administered 25 mg/kg each dissolved in 20% polyethylene glycol. Donepezil group was orally administered 2.25 mg/kg dissolved in saline. All treatments were continued daily for 4 weeks; afterward, the Morris water maze (MWM) test was initiated. Rats were euthanized 24 hours after probe trial for retention test; then brain tissues were collected from all groups for determination of pro-oxidants, antioxidants, an inflammatory marker, acetylcholine esterase activity, Alzheimer disease markers, and energy profile. Treatment with berberine/ipriflavone mixture improved scopolamine-induced cognitive dysfunctions in the MWM test and was significantly related to the increment in anti-oxidant levels, anti-inflammatory activity, cholinergic function, and brain energy profile. The current study revealed the relation between glucose-6-phosphate dehydrogenase and Alzheimer disease progression. Also, this mixture showed a substantial protective effect against the cognitive impairment induced by scopolamine.