Background The intrinsic adroitness of medicinal plants as a therapy for several maladies is well-documented in African Herbal Pharmacopeia. Leaves of Ficus aurea L. ( Moraceae) are commonly used in folkloric medicine in southeastern Nigeria and other areas of the world to treat malaria, dermatitis, circulatory and intestinal parasitic health abnormalities. Objective The aim of the study was to explore the phytochemical composition and potential toxicity of the ethanolic leaf extract of F. aurea L. (herein afterwards referred to as ELEFA) in albino rats of both sexes. Methods Gas chromatography mass spectrometry (GC–MS) was performed to analyze the chemical constituents of F. aurea. In the acute toxicity study, a single oral dose of up to 5000 mg/kg ELEFA was administered. For the sub-acute toxicity study, rats were randomly assigned to individual cages to eschew copulation. Male groups (A2-A4) and female groups (B2-B4) were administered varying doses of ELEFA (250, 500, 750 mg/kg) for 28 days, while control groups A1 and B1 received 1 mL/kg of distilled water. Standard analytical procedures were utilized to evaluate the biochemical and haematological profiles, as well as liver and kidney histopathology. Results The GC–MS analysis identified 13 phyto-compounds, six of which possess known bioactive and pharmacological properties. These bioactive compounds include gamma-dodecalactone, n-hexadecanoic acid, methyl stearate, 9,12-octadecadienoic acid, oleic acid, octadecanoic acid. In the acute toxicity, no death was recorded within 24 h following oral administration of ELEFA. Remarkably, haematological and renal biomarkers remained unaltered post-ELEFA administration. However, elevated levels of serum aspartate and alanine transaminases were detected in ELEFA-treated groups, indicating potential hepatotoxicity. A reduction in atherogenic lipid markers and a dose-dependent elevation in antioxidant concentrations were observed, suggesting a nuanced impact on oxidative stress. Conclusion The study emphasized caution regarding higher ELEFA doses, highlighting potential hepatotoxic effects evident in liver histopathology at 500 mg/kg and 750 mg/kg. We recommend the prudent use of lower ELEFA doses for therapeutic purposes to mitigate potential adverse effects.