Display omitted •Eleven phenolic compounds were reported for the first time from Ficus sycomorus.•Leaf and stem bark extracts displayed antioxidant and enzyme inhibition properties.•Bioinformatics analysis showed selective advantage of quercetin in tumorigenesis.•F. sycomorus could be a beneficial source of natural of bioactive agents. This study was aimed to determine the phenolic profile of the leaf and stem bark of Ficus sycomorus and to investigate their antioxidant and enzyme inhibition properties. Extracts were prepared by maceration with hexane and dichloromethane: ethanol (DE) (1:1) respectively. Phenolic content was quantitatively determined and their constituents were identified on the basis of co-chromatography with reference compounds. Results showed that the leaf displayed significant higher polyphenolic and flavonoid contents than the stem bark while the latter showed significant highest total tannin content.. The leaf DE extract exhibited significant higher antiradical activity and higher capacity to reduce Fe3+ than the stem bark DE extract. The leaf DE and stem bark hexane extracts significantly (p < 0.05) displayed the highest acetylcholinesterase and α-glucosidase inhibition while the former showed significantly (p < 0.05) the highest inhibition towards tyrosinase. Regarding the enzyme inhibition effects, the bioinformatics analysis suggested that the quercetin pool could be at the basis of the observed effects. Results obtained from this study suggested that, F. sycomorus could be a rich natural source of bioactive molecules with antioxidant and enzyme inhibition properties.