Two coumarinolignans, cleomiscosins C (1) and D (2) were isolated from the heartwood of Acer mono, together with four compounds, 5-O-methyl-(E)-resveratrol-3-O-b-D-glucopyranoside (3), 5-O-methyl-(E)-resveratrol-3-O-b-D-apiofuranosyl-(1?6)-b-D-glucopyranoside (4), scopoletin (5), and (E)-resveratrol-3-O-b-D-glucopyranoside (6). Of them, cleomiscosins C (1) and D (2) were applied to preparing inclusion complex molecules with b-cyclodextrin (b-CD) to improve the very poor solubility in cell media. The CD complexes of 1 and 2 exhibited an enhancement of water solubility which is feasible to measure their cytotoxicity using a spectrophotometer in a cell-based assay. Anti-proliferative activity of these complex molecules was successfully estimated on HCT116 human colon cancer cells, and cleomiscosin D (2) showed anti-proliferative effects at the concentration of 1.95~31.2 mg/mL in a dose-dependent manner.