Abstract Ethnopharmacological relevance Gouania longipetala leaves are commonly used in folkloric medicine in Africa and other parts of the world for treatment of edema, febrifuges, veneral diseases, lumbago, heart diseases, diabetes mellitus malaria, etc. This study therefore evaluated safety profile of the methanol leaf extract of the plant using acute and sub-chronic studies in rat model. Materials and methods Acute toxicity test of the plant lasted for 48h with oral administration of graded doses (100–4000mg/kg) of Gouania longipetala extract (GLE) in rats. The rats were observed for signs of toxicity and death. The sub-chronic toxicity was evaluated by administration of different doses (2.5, 5 and 10mg/kg) of GLE daily in feed for 90 days. On days, 30, 60 and 90, blood samples collected from the retro-orbital plexus of the eye of the rats were used for evaluation of serum biochemistry, hematology, lipid peroxidation and in vivo antioxidant activities. Histopathological evaluations of the kidney, liver, lungs and heart were also done. Results The acute toxicity test revealed no observable signs of toxicity or morbidity. Sub-chronic study showed that GLE significantly (p<0.05) increased relative liver weight on day 90 at 10mg/kg. There were no significant variations in the hematological parameters of both GLE treated and untreated rats. The extract significantly (p<0.05) reduced total cholesterol, triglycerides, very low density lipoproteins and increased high density lipoproteins which was more prominent on day 90 at the dose of 10mg/kg. The extract significantly (p<0.05) increased liver enzyme markers at the doses used. GLE also significantly (p<0.05) increased serum urea at the dose of 10mg/kg on day 90. The extract caused dose-dependent and significant (p<0.05) increase in superoxide dismutase and decrease in malondiadehyde. Histopathological studies revealed degenerative changes in the kidney and liver. Conclusion The results of the study suggest that Gouania longipetala is well tolerated in short term therapies, but may have long term toxic effects on the kidney and liver.