The content of bioactive compounds in Sargassum sp. already used in various fields. The Ultrasound Assisted Extraction (UAE) method and water solvent has met the principles of green chemistry so that it is used in this study as a method of extracting antioxidant compounds contained in Sargassum sp. The principle of green chemistry has the main goal of reducing or eliminating the impact of environmental damage. This research was conducted with several process variables, including the ratio of the sample mass to the volume of solvent (0.05 – 0.15 g/mL), time (30 – 40 minutes) and power (170 – 180 W) using the UAE method and water solvent (aquadest) on the total phenol value of Sargassum sp. result. Analysis of variance was carried out with the help of Design Expert software, Response Surface Method - Central Composite Design to determine the effect of the process variables carried out in the extraction process on the total phenol yield. The analysis of variance in this study shows the suitability between the research design and the results of the study which is indicated by an R2 value of 0.9785. The highest results were obtained with a variable ratio of sample mass to solvent volume of 0.18 (g/mL), time of 40 minutes and power of 180 W with a total phenol yield of 212.8 mg GAE/g and antioxidant activity of 12.3%.