Schimpera arabica (Safra), growing wild in Egyptian deserts and the northern region of Saudi Arabia, has not been extensively studied. The ethyl acetate fraction of S. arabica methanol extract revealed significant antioxidant capacity and cytotoxicity. The reversed-phase high-performance liquid chromatography of the ethyl acetate fraction contains a variety of phenolic compounds, including quercetin (6), luteolin-8-C-beta-D-glucopyranoside (10), trans-cinnamic acid (11), quercetin-3-galactoside (13), and naringenin-5,7-di-O-glucoside (15). The further cytotoxicity of ethyl acetate demonstrated a strong antiproliferative effect on the Huh-7 and HepG2 cell lines, with IC50s of 52.58 and 73.10 mu g/mL, respectively. The ethyl acetate fraction has a significant level of total phenolics (51.53 mg GAE/g extract) and total flavonoids (59.25 mg RE/g extract), according to a quantitative analysis of total phenolics. S. arabica may prove to be a viable source for the creation of natural antioxidants. High total phenolic and antioxidant activity suggests it may be a promising avenue for developing natural antioxidants. Molecular docking was carried out in the active site of NQO1. Naringenin 5,7-di-O-glucoside (15) showed the highest binding energy due to its intricate HB with the target protein.