Daniellia oliveri (DO) is a traditional medicinal plant used for the treatment of diseases such as inflammation, schizophrenia, and epilepsy in Nigeria, Kenya, Congo, and Cameroon. This study was carried out to evaluate the potential neuroprotection effect of the aqueous root bark extract of Daniellia oliveri against diazepam-induced amnesia in mice. Thirty-six adult male mice were distributed into six groups: the three test groups received Daniellia oliveri root bark extract (100, 200, and 300 mg/kg), the normal control group received distilled water (10 ml/kg), a positive control group received piracetam (150 mg/kg), and the negative control received diazepam (2.5 mg/kg). Learning and memory were evaluated using the radial arm maze and the T-maze. Biomarkers of oxidative stress were also quantified in mice brains. Statistical analyses were performed using two-way ANOVA followed by Tukey’s post hoc test. Daniellia oliveri root bark aqueous extract decreased the number of working memory errors and number of reference memory errors in amnesic mice evaluated in the radial arm maze. Also, an increase in glutathione activity and a decrease in malondialdehyde levels were noted in the hippocampi homogenate of the extract-treated mice as compared to the diazepam-demented but untreated group. Moreover, pretreatment with Daniellia oliveri aqueous root bark extract reversed the decrease in hippocampal cell density observed in the nontreated diazepam group. Taken together, these results suggest that the aqueous extract of DO leaves possesses antioxidant potential and might provide an opportunity for the management of neurological abnormalities in amnesic conditions.