Ethnopharmacological relevance Aloe rubroviolacea (Arabian Aloe) was widely cultured and commonly used in traditional medicine. Aloe species was highly recommended in folk medicine for abdominal pain, intestinal infection, intestinal colic, obesity, and gynaecological pain after childbirth. Aim of the work The present work aimed to conduct chemical profiling, in-vitro antioxidant activity, in-vivo oral acute toxicity study of A. rubroviolacea flowers ethanolic extract (ARFEE) along with exploring pancreatic and hepatic protective effects of ARFEE against carbon tetrachloride (CCl4) toxicity in a rat model. Molecular docking study of ARFEE and 3D structure activity relationship was also demonstrated to investigate the proposed antioxidant mechanism. Materials and methods The chemical composition was analyzed using gas chromatography-mass spectrometry (GC-MS) and thin layer chromatography (TLC) techniques. Total phenolic and flavonoid contents in ARFEE were estimated by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. In-vitro antioxidant DPPH assay was performed using ascorbic acid as a reference standard. Moreover, In-vivo acute toxicity study using fixed doses of ARFEE (0.1, 0.5, 1, 2 and 3 g/kg orally) was conducted. CCl4 toxicity was induced by using a single dose of CCl4 (1 ml/kg, i.p.) on 5th day, silymarin (50 mg/kg/day, orally) as a standard and two different doses of ARFEE (250, 500 mg/kg, orally) daily for 5 days before CCl4 injection. Results GC-MS analysis displayed the existence of 36 chemical compounds, the majority of which were fatty acids and their esters, in addition to phytosterols. The total phenolic content of ARFEE was 25.09 ± 1.65 mg of gallic acid equivalent/g extract dry weight (mg GAE/g DW), while the total flavonoid content was 17.48 ± 0.64 mg of quercetin equivalent/g extract dry weight (mg QE/g DW). Our results showed that the ARFEE had a potential in-vitro antioxidant activity as strong as ascorbic acid. No mortality or signs of toxicity were observed after ARFEE intake. Additionally, ARFEE ameliorated CCl4 toxicity on hepatic and pancreatic tissues. Molecular docking study resulted in potent promising natural compounds contained in ARFEE with anti-oxidant potential. Conclusion Based on oral safety, good anti-oxidant and pancreato- and hepato-protective activities of ARFEE against CCl4 toxicity, ARFEE is probably a potent agent for treatment of liver ailments.