Liquid chromatography-mass spectrometric (LC/MS) analysis of the leave’s methanol extract of Fortunella margarita (Lour.) Swingle led to the identification without isolation of four main compounds. Extensive chromatographic purification revealed the isolation of acacetin 7-neohesperidoside, acacetin 7-rutinoside and 4-(β-D-glucopyranosyloxy) benzoic acid. Proton Nuclear Magnetic Resonance (1H-NMR) and Carbon-13 Nuclear Magnetic resonance (13C-NMR) along with HR-ESI/MS were used to elucidate the chemical structure of the isolated compounds. Liver protection against DMN and/or CCl4-induced toxicity was evaluated for the ME of F. margarita, and the obtained results showed that the ME decreased the elevated liver enzymes to the normal level, indicating the protection of structural integrity of hepatocytic cell membrane or regeneration of damaged liver cells.