The plant Swietenia mahagoni has been used to treat many human ailments. Swietenia mahagoni leaf extract (SMLE) showed potential anti-leukemic, anti-inflammatory, analgesic and antipyretic activity in our previous study but in its activity on glioma cells have not been reported so far. Therefore, in this present study we evaluated the apoptosis inducing effect of SMLE on glioma cells. Cytotoxicity was studied by MTT assay and cellular morphology performed by fluorescence and confocal microscope. Detection of DNA fragmentation by electrophoresis and mitochondrial membrane potential assay by JC-1 dye. Cell cycle arrest by flow cytometric analysis had been performed to determine the proportion and stages of cellular apoptosis of C6 and U87MG cell lines. SMLE significantly inhibited the cell viability in a time and concentration dependent manner in both the glioma cells. After treatment with the extract, glioma cells, showed several signs of apoptosis like chromatin condensation, nuclear fragmentation and formation of apoptotic bodies than control cells and degraded DNA bands in cancer cells. Cell cycle phase arrest was observed in the G0/G1 phase in both the cancer cells. MMP shift assay exhibited significant change in the SMLE treated glioblastoma cells. These findings suggest that Swietenia mahagoni leaf extract possesses cytotoxic and apoptotic activity against glioma cells. Further mechanistic studies are under process to determine the different pathways attributing to apoptosis.