This study evaluated the in vitro and in vivo free radical scavenging potentials of methanol extract of Ficus thonningii leaf and its liquid chromatography-mass spectrometer (LCMS) profiling. The qualitative phytochemical screening was carried out and the results show the presence of tannins, flavonoids, saponins glycoside and triterpenes. Antioxidant activities were carried out in vitro and in vivo and the reducing power shows a value of 0.53 ± 0.007 with a significant (p < 0.05) difference compared to the control and Diphenylpicrylhydrazyl (DPPH) value of 59.0 ± 0.007 with a significantly different (p < 0.05) compared to the control. However, the two assays are concentration-dependent. The in vivo analysis shows that lipid peroxidation, superoxide dismutase and catalase activities have values of 24.03± 8.04, 1.60± 0.03 and 0.003± 0.001 respectively. All the values are significantly different when compared to the control and are concentration-dependent. The LCMS results revealed the presence of some important metabolites; phenolic glycosides and quassin, which are potential molecules against free radicals. Therefore, Ficus thonningii leaf contains vital antioxidants and could be used in health management to boost the immune system or in drug development.