Developing efficient and eco-friendly extraction methods is a major goal of the functional food industry. We developed an ultrasonication extraction method for Undaria pinnatifida sporophyll requiring 6 h extraction time at 80% amplitude. This application of ultrasonication increases yield by 25% and decreases extraction time by approximately 18 h. Additionally, we investigated the effect of the ultrasonicated sporophyll from Undaria pinnatifida extract (UPE) on LPS-induced inflammation. Following ultrasonication, the average molecular weight decreases in comparison to conventional methods, in a similar manner to commercial fucoidan. UPE significantly suppresses lipopolysaccharide (LPS)-induced nitrite and PGE2 production and subsequently suppresses inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in Raw 264.7 cells. Western blot assay results also demonstrate that UPE strongly suppresses LPS-induced c-Jun N terminal kinase (JNK) 1/2/MKK 4 and p38/MKK3/6 phosphorylation in Raw 264.7 cells. SR11302, an AP-1 specific inhibitor, suppressed LPS-induced iNOS and COX-2 expression. In addition, SiMLK3 strongly suppressed LPS-induced iNOS and COX-2 expression, as well as JNK1/2 and p38 phosphorylation in Raw 264.7 cells.Taken together, these results suggest that this ultrasonication extraction method is more efficient for extracting sporophyll of Undaria pinnatifida extract, which has potent anti-inflammatory properties.