The comb-like copolymers of polycarboxylic acid were synthesized and then reacted with chenodeoxycholic acid (CDCA) to obtain a series of conjugates, MP n–CDCA, where n is the number of the groups of oxyethylene in each graft chain. This was confirmed by infrared spectroscopy and thin-layer chromatography. We investigated the effects of dissolving model cholesterol gallstones with the MP n–CDCA conjugates in phosphate-buffered saline at pH 7.4. The dissolution rates of CDCA, MP40–CDCA, MP30–CDCA, MP20–CDCA and MP10–CDCA were 5.33, 5.717, 17.59, 6.868 and 9.615 × 10 −7 kg m −2 s −1, micellar solubilities were 0.2431, 3.095, 12.972, 5.248 and 5.790 kg m −3 and total resistances were 5.33, 5.717, 17.59, 6.868 and 9.615 × 10 −7 kg m −2 s −1, respectively. These studies suggested that the interfacial resistance was the dominant rate-determining factor in dissolving model cholesterol gallstones. Model cholesterol gallstones could be more effectively dissolved by increasing the steric interactive potential energy of side chains and ensuring that the hydrophilic–lipophilic properties of MP–CDCA are within an appropriate range. The micellar dissolution rates of model cholesterol gallstones by MP20–CDCA were significantly faster than by the other conjugates.