Exploring the oceans for bioactive compounds is an incessant human desire. The present study investigates selected bioactivities; anti-inflammatory, anti-oxidant, cytotoxic, and genotoxic potential of Axinella sp. marine sponge crude extract (SCE). Sponge identification was based on morphology and skeletal analysis. The SCE was prepared by methanol/dichloromethane extraction and tested for zoo-chemicals, anti-inflammatory properties by protein denaturation, heat and hypertonicity-induced bovine erythrocyte membrane stability assays. Radical scavenging activity was tested against 2,2-diphenyl-1-picryl-hydrazil (DPPH), 2,2′-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), nitric oxide (NO), and peroxide radicals. The IC50 was calculated for each assay. Cytotoxicity and genotoxicity were tested on Artemia salina and Allium cepa models, respectively. The LC50 and mitotic index (MI) were calculated where appropriate, while chromosomal aberrations were recorded in the A. cepa assay. The results indicated the presence of alkaloids, terpenoids, unsaturated sterols, flavonoids, and saponins in SCE. Potent inhibitory activities on egg albumin denaturation were reported by SCE (IC50=39.55±3.21 μg/ml). Heat and hypertonicity induced bovine erythrocyte membrane stability was reported as IC50=44.64±0.56 μg/ml and IC50=35.7±.0.26 μg/ml, respectively. In comparison to reference drugs, the resulting scavenging activities were strong against NO (IC50=50.63±2.85 μg/ml) and more or less similar against DPPH (IC50=42.49±0.85 μg/ml). However, the potency of ABTS and peroxide radical scavenging activities was low in SCE (IC50=42.49±0.74 μg/ml and IC50=323.52±3.71 μg/ml, respectively). The SCE was toxic to A. salina nauplii (LC50=106.81 μg/ml) and A. cepa root cells (LC50=114.63 μg/ml) with a 7.2% chromosomal aberrations reported in the A. cepa genotoxicity assay. The potent anti-inflammatory, anti-oxidant, cytotoxic, and genotoxic effects of SCE proposes its feasibility as a potential drug lead, followed by further comprehensive research.