Despite being the most common primary malignant tumor of the central nervous system, the prognosis of glioblastoma (GBM) is still remarkably poor. Paradol is a flavor phenolic constituent found in pepper and ginger, with anti-tumor, anti-inflammatory, and antioxidant activities. However, the effects of paradol on GBM cells remain unknown. In this study, we investigated the cytotoxicity of paradol on U-87 and U-251 GBM cells. Cell viability and Transwell assays revealed that paradol treatment markedly inhibited the viability and migration of GBM cells. Flow cytometry analysis showed G0/G1 cell cycle arrest, which was verified by the downregulation of CCNA and CCNB expression using western blotting. Paradol-induced cell apoptosis was confirmed by annexin V-FITC/PI staining and nuclear morphology. Furthermore, the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) was determined by western blotting. Collectively, our data revealed that paradol inhibited cell viability and migration of GBM cells by inducing G0/G1 phase arrest and apoptosis, and activating ERK and p38 MAPK signaling.