<p>Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumor with a poor median survival rate. The treatment for GBM is still challenging due to its heterogeneous microenvironment, which suggests that more therapeutics should be researched for effective treatment to increase patients’ survival. The naturally occurring compounds are known to inhibit the growth of cancer due to their multifaceted mechanism. Ellagic acid is found in fruits such as cranberries, vanillin is used in food as a flavor, carvacrol, and thymol are derived from terpenes, and hesperetin is found in citrus fruits. The purpose of this current study examined the inhibitory effect of phytocompounds (ellagic acid, vanillin, carvacrol, thymol, and hesperetin) in GBM cells, and in silico exploration of the target proteins for phytocompounds. The results showed the antiproliferative effect of vanillin, carvacrol, thymol, and ellagic acid reduced cell proliferation in U87MG and LN229 cell lines. The in-silico results identified EGFR as a target protein for ellagic acid and carvacrol in GBM. The docking results also showed favorable binding as analyzed by patchdock software. This research demonstrated that the phytocompounds ellagic acid, vanillin, carvacrol, and thymol had an inhibitory effect on GBM cells. Ellagic acid and carvacrol showed interaction with EGFR, indicating these compounds as inhibitors of EGFR. These phytocompounds could be a potential therapeutic for GBM.</p>