The current study investigated the toxicity of the ethanol extract of _Olea africana_ in mice and brine shrimp _(Artemia salina)_. Brine shrimp cytotoxicity and acute toxicity of the extract in mice were observed over 24 hours. Subacute toxicity of the extract was studied in mice for 28 days using animal weight, organ-to-body weight ratio, and hematological, biochemical and histological parameters as indicators. Data analysis was done using Probit regression and Two Way ANOVA _(p<0.05)_. The lethal concentration of the extract responsible for 50% mortality in brine shrimp (LC50) was 2257.84 µg/mL (702.97-7367.95), while the lethal dose of the extract responsible for 50% mortality in mice (LD50) was 4297.30 mg/kg. There were no significant differences in the mean weight or organ-to-body weight ratio of the control and treatment group mice. Some hematological and biochemical parameters in extract-treated mice were significantly different from control group mice. Adverse histopathological changes including fibrosis around the hepatic artery, degeneration of hepatocytes, congestion, and mild fibrosis around the portal vein and artery were observed in the livers of extract-treated mice. Perivascular infiltration, fibrosis, mild glomerular degeneration, mild tubular degeneration, cell infiltration, and hemorrhage were observed in the kidneys of extract-treated mice. Given these findings, prolonged administration of _Olea africana_ is associated with significant toxic concern. As a result, caution should be exercised when using the extract.