Background: Holarrhena antidysenterica is a deciduous shrub/small-tree having bioactive alkaloids such as conessine, known for astringent, antidysenteric, anthelmintic, stomachic, febrifugal, tonic and anti-acetylcholinesterase properties. Dementia is an age related neurodegenerative syndrome with Alzheimer’s disease, the most prominent cause, which has limited therapeutic options available.Objective: The present study aimed to explore the potential benefits of H. antidysenterica in the management of dementia. Methods: Aqueous and methanol extracts of powdered bark of H. antidysenterica were prepared, concentrated and conessine concentration was estimated using High Performance Thin Layer Chromatography (HPTLC) method. Methanol extract of H. antidysenterica (MEHA) was administered at doses 100, 150 and 200 mg/kg (i.p.) to mice (20-30 g) for 14 consecutive days. Scopolamine (Scop; 1 mg/kg) and Lipopolysaccharide (LPS; 250 μg/kg) were given (i.p.) before behavioural trials to induce memory impairment. Learning and memory functions in mice were evaluated. Brain acetylcholinesterase (AChE) activity, glutathione (GSH) and Thiobarbituric Acid Reactive substances (TBARS) levels were estimated. Results: MEHA markedly increased learning and memory of mice. Scop or LPS caused a significant decline of spatial memory in mice, which was attenuated by MEHA (100 and 200 mg/kg). Furthermore, LPS conspicuously increased the lipid peroxidation and compromised antioxidant levels in mice brains. MEHA pre-treatment significantly increased GSH content and decreased TBARS level in the brain of LPS administered mice. AChE activity was significantly decreased by MEHA in the brain of mice. Conclusion: The methanol extract of H. antidysenterica may prove to be a useful remedy in the management of dementia.