Background: Grewia flavescens Juss (Malvaceae) is a species that is distributed throughout semi-arid and sub-humid tropical areas of Africa, Saudi Arabia, Yemen, and India. It is used in various traditional herbal practices for the treatment of various disease conditions. Objectives: The present investigation was undertaken to examine the immunomodulatory and cytotoxic properties of natural triterpenoids isolated from the stem bark of G. flavescens. Materials and Methods: The immunomodulatory activity was measured using oxidative burst chemiluminescence and phytohemagglutinin stimulated T-cell proliferation assay. The cytotoxicity was measured using MTT assay. One new triterpenoid (29 -lupene-3, 20-diol; 3 β-form, 29-Aldehyde ) in addition to four known ones; lupeol (1), ß-sitosterol (2), betulin (3), and ß-sitosterol glucopyranoside (5), have been isolated from the stem bark of G. flavescens and identified using Fourier-transform infrared spectroscopy, ultraviolet, and NMR techniques. Results: Chemiluminescence experiments showed that no compound exerted an inhibitory effect on reactive oxygen species production. However, 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde (4) significantly repressed the cell proliferation activity with an IC50 of 8.7 μg/mL, whereas, ß-sitosterol glucopyranoside (5) and ß-sitosterol (2) showed moderate inhibitory activities (IC50 of 16.7 and 23.6 μg/mL, respectively) compared to the standard drug prednisolone (0.2 μg/mL). Betulin (3) revealed the highest cytotoxicity activity toward Hela cancer cells, followed by 29 (30)-lupene-3, 20-diol; 3 β-form, 29-Aldehyde (4), and ß-sitosterol (2) with IC50 11.10, 16.5 and 21.51 μg/ml respectively. Conclusion: The present investigation supports the traditional use of this plant in treating various diseases and it has a good potential for future studies based on animal model based, which could bring more mechanistic facts about this plant's activity.