In our consecutive research on an anti-AD remedy derived from maritime plants, the BACE1 inhibitory activities of Eisenia bicyclis and its isolated phlorotannins were evaluated. The E. bicyclis extract and its fractions exhibited predominant BACE1 inhibition. With the exception of phloroglucinol (1), all test phlorotannins isolated from the most active EtOAc soluble fraction, showed significant and non-competitive inhibition against BACE1:dioxinodehydroeckol (2, IC(50)=5.35 microM; K(i)=8.0); eckol (3, IC(50)=12.20 microM; K(i)=13.9); phlorofurofucoeckol-A (4, IC(50)=2.13muM; K(i)=1.3); dieckol (5, IC(50)=2.21 microM; K(i)=1.5); triphloroethol A (6, IC(50)=11.68 microM; K(i)=12.1); 7-phloroethol (7, IC(50)=8.59 microM; K(i)=7.2). In addition, plausible protein-ligand interactions of 3, 4, and 5 were similar and may occur primarily through the TYR132 and THR133 of BACE1 via molecular docking simulations (autodock 4.0 and fred 2.0 programs). As a result, the E. bicyclis extract and the phlorotannins contained therein would clearly have beneficial use in the development of therapeutic and preventive agents for AD and suggest potential guidelines for the design of BACE-selective inhibitors.