A series of Albiziabioside A coupled substituents of cinnamoyl derivatives were designed and synthesized. The synthesized compounds were screened for anticancer activity against a panel of six human cancer cell lines using a MTT assay. Synthetic derivatives showed excellent selectivity, as they were toxic against only HCT116 cell line. Some compounds exhibited better anti-cancer activity against HCT116 compared to positive controls, such as 5-fluorouracil and Albiziabioside A. Compound 8n was the most active derivative. Importantly, it was also found that the anti-proliferative activity of 8n could be attributed to the induction of cell cycle arrest and apoptosis in HCT116 cells.