Twenty novel noscapinoid-triterpene conjugate derivatives were designed and synthesized. Four noscapine derivatives (as secondary amine) and five bile acids were applied for the synthesis of a diverse library. The synthetic compounds were evaluated for their antiproliferative activity against PC3, A549, HepG2, Caki-1, U138MG, and MRC5. This study identified eight potent cytotoxic agents (7e-7i, 7k, 7m, and 7o) possessing more than 80% cell viability. Compounds 7e and 7f exhibited the highest cytotoxic activity against Caki-1 with IC<inf>50</inf> values of 260 nM and 350 nM, respectively. Western blot analysis results indicated that the eight hit compounds decreased the α-tubulin and β-actin levels in A549 cells, and further cellular assays on A549 demonstrated that 7e and 7f significantly inhibited cell migration, induced pronounced G1 cell-cycle arrest (with 7f also showing a minor G2/M increase) and triggered marked apoptosis, with 7e showing the strongest pro-apoptotic effect.