Crocus sativus ( C. sativus) is considered as the costliest spice and an important medicinal plant. Herein, we investigated the effects of tepal extract (TE) of C. sativus on the viability of the human glioblastoma cells. Results revealed that TE significantly ( P < 0.05) inhibited the proliferation of U87 glioblastoma cells in a dose-dependent manner with comparatively lower toxic effects against normal astrocytes. The IC 50 of TE against U87 glioblastoma cells was found to be 130 μg/mL as compared to 600 μg/mL against normal astrocytes. TE also inhibited the colony formation of U87 cells significantly ( P < 0.05). The AO/EB and Annexin V/PI staining assays indicated that TE stimulated apoptosis in U87 cells dose dependently. The early and late apoptotic U87 cells increased from 0.66% and 2.3% at control to 14.2% and 21.4% at 260 μg/mL of TE. Moreover, TE caused upregulation of Bax and suppression of Bcl-2. Wound healing assay showed that migration of the U87 cells was suppressed significantly ( P < 0.05) at 80 μg/mL of TE. Taken together, these results suggest that TE exhibits antiproliferative effects against U87 glioma cells and may prove to be an important source of natural anticancer agents.