Background & Aim:Citrus paradisi Macfad (Rutaceae) seed extract (CPE) is used in folkloric medicine for the management of diabetes, blood deficiencies and as immune booster, which may require long term usage. This study aimed to evaluate the toxicity profile of ethanol seed extract of grapefruit in adult Wistar rats in order to determine its safety profile in whole organism’s systems.Experimental: Acute toxicity study was conducted using OECD–425 procedure. Subchronic toxicity study (90 days) was conducted using 40 adult male Wistar rats, randomly divided into four groups (10/group) and orally-treated daily, thus: Group I-Control (normal saline, 10 ml/kg), Groups II-IV received CPE (4, 40 and 400) mg/kg body weight, respectively. On the 92nd day, animals (6/group) were euthanized under diethyl ether anaesthesia and sacrificed. Vital organs were eviscerated, blotted, weighed and stored for oxidative stress measurement; some samples of the organs were fixed in formalin for histopathological examination. Other animals (4/group) were retained for reversibility studies.Results: Results showed significant increase and decrease in weights of the kidneys and spleen, respectively. Significant increase in malondialdehyde level and decreases in superoxide dismutase, glutathione and catalase activities were recorded. Histopathology of the kidney, liver, and lungs showed some degree of pathologies. Reversibility studies showed reversal of test effects on extract discontinuation. Despite the diverse biological usefulness of ethanol seed extract of C. paradisi (CPE), it may also induce an array of toxicities especially on long term use.Recommended applications/industries: Contrary to the tradomedical claims that CPE is absolutely safe, the study revealed that CPE may induce oxidative stress and organ toxicity especially on long term use. It is imperative the plant seed extract and its derivatives be used with utmost caution, and where possible be avoided. Manuscript profile