This study aimed to investigate anti-inflammatory effects of Ruta graveolens and Pegenum harmala extract in management of neuroinflammatory insults characteristic for Alzheimer's disease (AD) in adult male rat. Rats were classified into (1), control group; (2), AD group, orally administered with AlCl3 (17 mg/kg b.wt.) daily for one month; (3), AD group, treated with rivastigmine (0.3 mg/kg b.wt.) daily for three months; (4), AD group divided into two subgroups each one treated with 750 mg/kg b.wt. of Ruta graveolens and 375 mg/kg b.wt. of Pegenum harmala daily for three months and (5), AD group divided into two subgroups each subgroup treated with 375 mg/kg b.wt. of Ruta graveolens and 187.5 mg/kg b.wt. of Pegenum harmala daily for three months. Brain acetylcholine (Ach) & serum and brain acetycholinesterase (AchE) activity, C-reactive protein (CRP), total NF Kappa B65 (NF-kappa B65) and Cyclooxygenase 2 (COX 2) levels were estimated. The results showed that administration of AlCl3 revealed significant elevation in AchE, CRP, NF-κB, and COX 2 levels and significant depletion in Ach level. Treatment with the selected extracts caused marked improvement in the measured biochemical parameters. In conclusion, Ruta graveolens and Pegenum harmala have a potent anti-inflammatory effect against neuroinflammation characterizing AD.