A new water-soluble inclusion complex of ilexgenin A (IGA) with β-cyclodextrin polymer (CDP) was prepared by a facile strategy and characterized by ¹H NMR , FT-IR, and UV-vis spectroscopy. Compared with IGA and the inclusion complex of IGA with β-cyclodextrin (IGA–CD), the solubility of IGA–β-cyclodextrin polymer (IGA–CDP) was greatly enhanced due to the water-soluble CDP host. The ratio of β-cyclodextrin (β-CD) units in CDP to IGA was determined as 2 : 1. K_D of the inclusion complex was evaluated as 2.6 × 10⁻³ mol L⁻¹. The effects of IGA–CDP on a hyperlipidemia mouse model were studied by intragastric administration. After 4 weeks, the IGA–CDP treatment resulted in decreased serum levels of total cholesterol and low-density lipoprotein-cholesterol. The effects of IGA–CDP on serum apolipoprotein levels were similar to its effects on lipid levels. By comparing liver area, the effects of IGA–CDP on pre-existing lesions were assessed. Furthermore, the efficacy and potency of water-soluble inclusion complex of IGA–CDP was 2–3 times higher than that of IGA. Taken together, it was possible to develop it to a novel drug candidate to regulate lipid abnormality.