Abstract Background Eragrostis tremula Hochst. ex Steud. (Poaceae) is used in ethno-medicine as a memory enhancer. Studies have shown that the whole plant possesses memory enhancing potentials and could be beneficial in the management of amnesia and cognitive deficit. Aim This study was aimed at investigating the actions of E. tremula extract on diazepam-induced amnesia in mice. Acute toxicity profiling was done as stated by the Organization for Economic Co-operation and Development (OECD 425). Oral doses of 125, 250 and 500 mg/kg of E. tremula extract were used for the diazepam-induced amnesia studies. Cognitive function was evaluated using elevated plus maze (EPM) and novel object recognition tests (NORT). The brain tissues were evaluated for the concentrations of malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) using enzyme-linked immunosorbent assay kits. Results The oral median toxic dose of E. tremula extract was assessed to be > 5000 mg/kg in mice. The extract substantially (p < 0.05) reduced the transfer latency of mice during the retention phase of EPM test. In the NORT, E. tremula extract at all the doses appreciably (p < 0.05) reduced the exploration time on the familiar object. Also, it substantially (p < 0.05) improved the recognition index. E. tremula extract substantially (p < 0.05) reduced the MDA levels, and at doses of 250 and 500 mg/kg, it prevented the cortical and hippocampal tissues from lesions produced by diazepam. Conclusions Eragrostis tremula extract is practically safe after acute administration and possesses anti-amnesic actions.