Background: Given the vast medicinal properties of Ocimum gratissimum, the present study evaluated, in comparative terms, the acute dysfunctional status of hepatorenal tissues of Wistar rats administered with petroleum ether (PE) and ethyl acetate (EA) leaf extracts of O. gratissimum. Methods: Grouping of the experimental rats was assigned according to the treatments given, in which graded doses {200, 400, 600 and 800 mg/kg body weight (b.w.)} of PE and EA fractions of O. gratissimum leaf extract were administered to the rats by oral gavage on a daily basis for a period of 21 days. Serum levels of hepatorenal tissues biomarkers were measured using standard spectrophotometric methods. The organ-to-body weight ratio of the rats was measured on the 21st day of the experiment. Results: Serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (i.e. AST/ALT) of the experimental rat groups was found to be within the range of 0.919 – 1.022 unit. The experimental rat groups administered with PE and EA fractions of O. gratissimum leaf extract showed dose-dependent increasing levels of serum alkaline phosphatase (ALP) activity. Likewise, rat groups administered with the herbal extracts exhibited increasing serum total bilirubin, urea and creatinine concentrations, in a dose-dependent manner. At the end of the 21-day treatment period, all the experimental rat groups showed increase in body weight, ranging from 0.79 – 1.98% increase. The liver weight and kidney weight to body weight ratios were within the range of (0.0468 0.02 – 0.0981 0.04) unit and (0.00245 0.002 – 0.01968 0.007) unit, respectively. Conclusion: The results showed that doses of PE and EA fractions of O. gratissimum leaf extract greater than 400 mg/kg b.w. induced dose-dependent hepatorenal toxicity, with the EA fraction provoking greater toxicity than the PE fraction of O. gratissimum leaf extract.