Polymeric micelles of curcumin were obtained using Pluronic P123 to increase the solubility and bioavailability of curcumin. The curcumin-P123 micelles were prepared by a thin-film dispersion method and the content of curcumin was determined by high-performance liquid chromatography. The entrapment efficiency was optimized by an orthogonal design to determine the best preparation method. The microscopic morphology, diameter, and drugloaded amount of the micelles were determined by transmission electron microscopy, particle size distribution, Fourier transform, and X-ray diffraction. The in vitro drug release rates were measured by a dialysis method. The entrapment efficiency of curcumin was 94.7% and the loading capacity was 3.06% under optimized conditions (curcumin 5 mg, Pluronic P123 150 mg, water 10 mL, and methanol 10 mL). The average size and zeta potential of the round or ellipse polymeric micelles were 117.23 ± 2.57 nm and 7.87 ± 2.50 mV, respectively, with uniform particle size distribution. The polymeric micelles were dispersed into block copolymers in molecular and amorphous forms based on X-ray diffraction and FTIR analysis. The polymeric micelles of curcumin showed significant sustained drug release in vitro compared with a pharmaceutical solution. The anti-tumor efficacy of curcumin-P123 on B16 cells was assessed in vitro by a (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The antitumor effects of the polymeric micelles was higher than that of curcumin. The prepared curcumin-P123 micelles increased the drug solubility in the aqueous phase. The polymeric micelles of curcumin have an important effect and excellent research value because of their sustained drug release and excellent inhibitory effect on tumor cells.