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The Eremobium aegyptiacum (Spreng.) Schweinf.et Asch.ex Boiss aqueous extract (EAAE) was subjected to phytochemical investigation using LC–ESI–MS analysis. Twenty-seven compounds (one organic acid, two phenolic acids and twenty-four flavonoids) were characterized and tentatively identified. Among the detected compounds, acyl triglycoside derivatives of kaempferol and isorhamnetin are identified in the current study by using LC–MS technique for the first time from this species. EAAE was evaluated for its anti-Alzheimer activity. EAAE dose (156 mg/kg bw/day) was administrated for 6 weeks orally to female adult rats prior treated with AlCl3 (50 mg/Kg b.wt) to induce Alzheimer disease. AChE level, lipid profile (TC, TG and LDL-C) levels, reduced glutathione (GSH) and malondialdehyde (MDA) levels were investigated. EAAE exhibited significant reduction in AChE level (58.57 ± 9 µMSH/min/mg protein) in comparison with AlCl3 group (97.88 ± 9.87 µMSH/min/mg protein). Also, GSH level was increased to 100.09 ± 25.51 mg/g tissue and MDA level was decreased to 1.26 ± 0.1 µmol/g tissue, compared to AlCl3 rats (57.05 ± 12.56 mg/g tissue and 1.96 ± 0.29 µmol/g tissue, respectively). Additionally, lipid profile (TC, TG, LDL-C) levels were significantly reduced to 35.15 ± 4.74, 18.16 ± 3.07 and 35.75 ± 4.17 µmol/g tissue, in comparison with AlCl3 group (65.20 ± 5.54, 27.93 ± 3.51 and 63.84 ± 6.98, respectively). Briefly, EAAE succeeded in amelioration of the increased AChE activity and the antioxidant activity which considered as an important defense mechanism to control the brain injury in AlCl3 rats. This amelioration was parallel to its effect on total cholesterol triglycerides and LDL levels.