Abstract: The phytochemical constituents and some neuropharmacological activity of the methanolic leaf extract of Cissus cornifolia (Bak.) Planch [Family: Vitaceae] was evaluated in mice employing various models. The preliminary qualitative phytochemical analysis carried out on the methanolic leaf extract of Cissus cornifolia revealed the presence of alkaloids, flavonoids, saponins, steroids/terpenoids, stilbenoids and tannins. The neuropharmacological effects of the methanolic leaf extract of Cissus cornifolia on CNS were evaluated using diazepam sleeping time, exploratory behaviour (head dip tests), motor coordination and acute toxicity studies in mice. The extract at tested doses (10, 20 40 mg kg-1 body weight i.p.) produced reduction in exploratory behaviour (head dip test), beam walking assay (foot slips) and potentiate the diazepam-induced sleep in mice; the LD50 was found to be 775.0 mg kg-1 body weight i.p. in mice. These results corroborates with the traditional usage of this plant as a remedy against mental derangement as confirmed by the sedative activity expressed by the extract.