This study aimed for investigating chemical constituents and biological activities of Diospyros zenkeri (Gürke) F. White. 14 known secondary metabolites have been isolated from the leaves and the twigs of D. zenkeri such as 3-methoxy-7-methyljuglone (1), β-carotene (2), lupeol (3), mixture of β-sitosterol (4) and stigmasterol (5), betulin (6), ursolic acid (7), messagenin (8), 3β,28,30-lup-20(29)-ene triol (9), mixture of the glucosides of stigmasterol (10) and β-sitosterol (11), norbergenin (12), betulinic acid (13) and vanillic acid (14), respectively . The structures of the compounds were elucidated with the help of NMR and mass spectral studies. The compounds 8, 9 and 14 are reported for the first time from the genus Diospyros. The biological screening of all the isolates and the crude methanolic extracts have been carried out including antiproliferative activity, antioxidant potential and inhibitory activity against the enzymes lipoxygenase and urease, respectively. Compound 1 exhibited significant antiproliferative activity against two cancer cell lines CAL-27 (IC50=2.98 μM) and NCI-H460 (IC50=5.57 μM). Methanolic extracts of the leaves and twigs of D. zenkeri presented low antiproliferative activity against these two cancer cell lines. Compounds 1, 6, 8, 9, 12 and the crude extracts exhibited moderate antioxidant activity with IC50 values of 76.5 μM, 65.8 μM, 55.3 μM and 51.2 μM respectively compared to BHA (IC50=44.2 μM). Compounds 6, 8 and 9 showed moderate lipoxygenase inhibition activity with IC50 values of 58.5 μM, 52.8 μM and 58.8 μM, respectively compared to baicalein (IC50=22.6 μM). Manuscript profile