AIM: To investigate the antitumor effects of ferulic acid (FA) on glioblastoma multiforme (GBM) cells both alone and in combination with temozolomide (TMZ), and also to determine the potential of this synergy for treatment processes. MATERIAL and METHODS: Human glioblastoma U87-MG cells were used in this study. To evaluate the potential constructive interaction between temozolomide (TMZ) and ferulic acid (FA), a sequential treatment protocol was applied in which cells were first treated with TMZ (20, 40, and 80 μM) for 48 hours, followed by FA (1000 μM and 1500 μM) for an additional 24 hours. Cell viability was assessed using the MTS assay, clonogenic capacity was evaluated by the clonogenic assay, and nuclear morphological changes were examined by Hoechst 33258 staining. The expression levels of Cyclin D1 and PARP were also analyzed to explore the molecular mechanisms underlying the treatment effects. RESULTS: FA treatment reduced cell viability and increased DNA damage in U87-MG cells. It suppressed the expression of Cyclin D1 and PARP. Furthermore, the combination of FA and TMZ almost completely inhibited cell proliferation and colony formation and significantly increased DNA damage. CONCLUSION: Although FA has demonstrated antitumor activity at high concentrations, this may limit its clinical applicability. However, its ability to enhance the effects of TMZ suggests that FA could be used as a supportive treatment strategy in GBM therapy.