Functional regulation of a protein complex is generally difficult because information of the target complex as a whole is limited. However, regulation of a protein complex is important for understanding complicated biological events in cells and therapeutic possibilities. This concept article introduces the potential for the functional regulation of a multiprotein complex, polycomb repressive complex 2 (PRC2), by developing chemical modulators. Functional regulatory mechanisms of PRC2 are described by using protein interaction information found through structural analyses. Subsequently, possibilities of novel chemical modulator development of PRC2 based on structural insights into the complex and related interactions are discussed.