The solvent extracts of Sargassum muticum, which were extracted by using several solvents with different polarities, were prepared for use as natural preservatives. The S. muticum extract with 80% ethanol was sequentially fractionated with n.hexane, dichloromethane, ethylacetate, and butanol. In order to effectively screen for natural preservatives agents, we first investigated the antioxidant activities such as DPPH radical scavenging capacity, superoxide radical scavenging capacity, and xanthine oxidase inhibitory activity of the S. muticum extracts. Through the screening system, we found that dichloromethane and ethylacetate fraction had high antioxidant activity with increments of the extract concentration. The antimicrobial activities and cell growth inhibition were investigated for each strain with the different concentrations of S. muticum extracts. Antimicrobial activities were shown in ethanol, dichloromethane, and n.hexane fractions of S. muticum. However, butanol, ethylacetate and water fractions showed weak antimicrobial activity against the tested microorganisms. Among the five fractions, dichloromethane fraction showed the highest antimicrobial activities against microorganisms tested, such as Bacillus sublitis, Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Salmonella Enteritidis and Pseudomonas aeruginosa. The polyphenolic compounds from ethanol, n.hexane, dichloromethane, ethylacetate, butanol, and water fractions were 63.96 mg/g, 8.49 mg/g, 28.11 mg/g, 172.64 mg/g, 114.56 mg/g, and 34.91 mg/g, respectively. The dichloromethane fraction could be suitable for development as a food preservative.