The present study focused the dose dependent protective effects of water extract of Benincasa hispida (BH) pulp on colchicine induced experimental rat model of Alzheimer`s disease (AD). The effect of chronic oral treatment of aqueous pulp extract of BH (400 mg kg-1 b.wt.) was studied in Holtzman strain adult albino rats of both sexes. The behaviour study, antioxidant level Superoxide dismutase (SOD), Catalase (CAT), Reduced glutathione level and Lipid peroxidation level were studied in different brain areas such as cerebral cortex (CC), cerebellum (CB), midbrain (MB), caudate nucleus (CN) and pons and medulla (PM) in colchicine induced experimental Alzheimer rat model before and after treatment with BH. Results indicate that chronic treatment with BH at different doses (100, 200, 300, 350, 400 and 450 mg kg-1 body weight), BH increased the CAT, SOD, GSH level and the number of correct choices out of 10 daily trials along with decreased latency time (in seconds) and LPO level dose dependently. These changes were statistically significant in some doses not in all doses. The effect of BH was most effective at 400 mg kg-1 body weight, compared to other doses on all parameters of different brain parts of colchicine induced Alzheimer`s rat model. Antioxidant plays a crucial role in the management of neurodegenarative diseases including Alzheimer`s disease. A number of Indian medicinal plants have been used in the traditional system of medicine (Ayurveda) for the management of neurodegenarative diseases including Alzheimer`s disease. Some of these plants have already been reported to possess strong antioxidant activity. BH, a fruit of common use, is rich in vit-E, beta-carotene, flavonoids and flavonols. Colchicine produces Reactive Oxygen Species (ROS) by binding with tubulin, which is the structural and functional protein of microtubule and ultimately helps in neurodegeneration leading to experimental AD. The results convey the message that at a dose of 400 mg kg-1 body weight BH has protective effect on colchicine induced Alzheimer`s disease.