Apoptosis is the most desirable target mechanism for induction of cell death in tumor cells. In this study three potent sponges such as Sigmadocia carnosa, Clathria gorgonoides and Callyspongia sp. were evaluated for their apoptosis regulating efficacy. These sponges were collected, extracted with methanol for bio-toxicity screening. The apoptotic inducing ability of sponge extracts have been evaluated using different bioassays. Various activities such as antimicrobial, biotoxicity and cytotoxicity were studied. Sigmadocia carnosa extract strongly inhibited Human leukemia cell lines (ATCC CCL-2), and was non-toxic to normal cells. It was cleared by all the results of tested bioassays such as MTT cytotoxicity, Hydrogen Peroxide Scavenging assay, DPPH Radical scavenging assay, COMET assay (Single cell electrophoresis), Trypan blue exclusion cell viability assay and DNA Fragmentation assay. In conclusion methanolic extract of Sigmadocia carnosa offers a valuable candidate lead compound to counter growing drug resistance in cancers.