Bridelia ferruginea is a woody shrub that grows in the Savannah or rain forests of Africa and has traditionally been used to treat diabetes, arthritis and boils. Despite all these uses, extensive toxicological evaluation has not been carried out. The aim of the present investigation was to evaluate the sub-chronic toxicological effects of the stem bark aqueous extract of Bridelia ferruginea in rats. The lethal dose (LD50) was determined using probit analysis and graded doses of the extract (250–4 000 mg/kg) were administered to the animals via oral and intraperitoneal routes and observed for mortality, behavioral changes and signs of toxicity. Sub-chronic toxicity study was carried out at doses of 1 000, 2 000 and 4 000 mg/kg administered daily for 60 days. The animals were sacrificed after 60 days. Blood was collected for biochemical (renal and hepatic), hematological, oxidative stress, sperm and histopathological examinations, using standard methods. LD50 of the extract was estimated as >4 000 mg/kg orally; neither significant visible signs of toxicity nor mortality were observed. There were no significant differences in the animals and organ weights, hematological and biochemical parameters in the treated groups compared to the control group. However, a significant increase (p<0.05) in the level of lipid peroxidation and a significant (p<0.05) decrease in sperm count were observed in the treated animals compared with the control group. The stem-bark aqueous extract of Bridelia ferruginea was found to be relatively safe, though it has the potential to cause lipid peroxidation and damage sperm quality and should thus be used with caution.