Since the oxidation of low-density lipoprotein (LDL) is one of the main causes of atherosclerosis, Cu2+-induced LDL oxidation and conjugated diene formation is currently being explored for the development of pharmaceutical drugs or functional foods for the treatment of atherosclerosis. The present work investigated the inhibitory effects on in vitro Cu2+-induced human LDL oxidation and conjugated diene formation of the methanol (MeOH) extract of the edible brown alga (Ecklonia stolonifera) and its different solvent-soluble fractions, as well as the phlorotannins isolated from them. The most active ethyl acetate fraction was selected for chromatographic separation to isolate six phlorotannins: phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofucofuroeckol A (4), dieckol (5), and 7-phloroeckol (6). Compounds 3–6 showed potent inhibitory activity against Cu2+-induced LDL oxidation as compared with probucol, a well-known clinical therapeutic agent for hypercholesterolemia. Moreover, when compound 5 (at levels of 9 and 4.5 μM) was used in combination with probucol (4.5 μM), they additively inhibited Cu2+-induced LDL oxidation. In addition, 3–5 significantly prolonged the lag time of conjugated diene formation at 10 μM. These results suggest that the potent antiatherosclerotic effects of E. stolonifera and its isolated phlorotannins may be partly attributed to the inhibition of Cu2+-induced LDL oxidation and conjugated diene formation.