Sea urchins can be used in medicine, has potential as a new type of antibiotic to developed in the pharmaceutical field, which is rich in bioactive compounds as a steroid, triterpenoids, saponins, and antioxidant properties. Conventional extraction generally takes a long time, is less environmentally friendly, and potentially triggers bioactive compound damage, so it needs alternative methods such as Ultrasound-Assisted Extraction (UAE). The extracting technology, including ultrasonic-assisted extraction (UAE) and solvent variation (ethyl acetate and methanol) of bioactive compounds from sea urchin (Diadema setosum) were optimized and compared. The purpose of this study was to study the application of UAE and solvent variation methods for sea urchin extraction from the Barrang Lompo Island in South Sulawesi. Comparing the maceration and ultrasonic assisted extraction methods. Optimization of extraction with UAE was carried out on the variable of extraction duration and type of solvent. Gas Chromatography-Mass Spectrometry results show that ultrasound-assisted extraction generally produces compounds of CHOLEST-5-EN-3-OL (3. BETA.), palmitic acid, 9-Octadecenoic acid (Z)-, methyl ester, stearic acid, oleic acid, flavonoids, phenols, pentadecanoic acid and batilol and streoid, which has a function as an antioxidant, anti-inflammatory, anti-tumor, anti-cancer agents and antibacterial. The results showed the best results using ultrasound-assisted extraction with a duration of 30 minutes and using solvent ethyl acetate. These results implied that extracts obtained by sonication showed the highest bioactive compounds and antioxidant activity, thus proving that this activity depends directly on the antibacterial properties.