In this work, alkyl methacrylate-based microgels were synthesized by an experimental design method, and their sebum absorption characteristics were investigated. The results of fractional factorial experimentation indicated that the cross-linking agent content, solvent content, and stirring speed were the main parameters in the synthesis of the microgels. The suitable synthesis conditions were determined by the response surface design method. Through a study of the monomer and solvent effects, it was confirmed that the microgel shows the highest sebum absorption ratio when t-butyl methacrylate is used as a monomer or when acetone is used as a solvent. The optimal microgel synthesis conditions for cosmetic application were determined, and the resulting microgel had a mean particle size of 4.7 μm and a sebum absorption ratio of 435%.