The invention relates to a preparation method and application of oral micelle microspheres. The problems that existing medicine is low in bioavailability when taken orally, poor in adsorption and large in toxic and side effect and causes stomach discomfort due to burst release of the medicine can be effectively solved. The preparation method includes the steps that PEG5000-PLGA5000 and granulesten are dissolved to serve as the water phase, 2-ME is ultrasonically dissolved in methyl alcohol, and the mixture is added into the water phase dropwise to obtain micelle suspension; carboxymethyl chitosan is prepared into a carboxymethyl chitosan solution with ultrapure water, polyacrylic resin is prepared into a polyacrylic resin solution with a phosphate buffer solution, and the carboxymethyl chitosan solution and the polyacrylic resin solution are mixed to obtain a microsphere material mixed solution; the micelle suspension and the microsphere material mixed solution are magnetically stirred and diluted in a 1-3 fold mode with the ultrapure water, and the micelle microspheres are obtained through spray drying. Intestine targeted control release of medicine carrying micelles can be realized, the intestine absorption time of the micelles is prolonged, the absorptivity to the medicine carrying micelles of the small intestine is improved, oral bioavailability of the medicine is obviously improved, and the medicine efficacy is improved.