Phytochemical investigation of Acer okamotoanum leaf and twig led to the isolation of two cou-marinolignans, cleomiscosin A (1) and cleomiscosin C (2). Here, we found that 2 dose-depen-dently inhibits LDL oxidation mediated by either catalytic copper ions (Cu2+) or free radicals generated with the azo compound 2,2'-azobis-(2-amidinopropane)dihydro-chloride (AAPH) with lC50s of 29.5 and 11.9 μM, respectively. By electrophoretic analysis, we also observed that 2 protects apolipoprotein B-100 (apoB-100) against Cu2+-induced fragmentation (65.3% inhibition at 5 μM). Furthermore, fluorescence analyses clearly indicated that both 1 and 2 protect against the oxidative modification of apoB-100 induced by either Cu2+ or HOCl (1, lC50s of 13.4 and 8.1 μM, respectively; 2, lC50s of 23.6 and 3.9 μM. respectively). These findings suggest that 1 and 2 could be beneficial in preventing LDL oxidation in atherosclerotic lesions.