In this study, indomethacin-functionalized linear polyglycidol micelle (INPG) was synthesized concurrently with its non-indomethacin containing counterpart (HDPG) as the reference. This innovative material was designed to deliver drug molecules with high selectivity and efficiency by integrating the COX-2 targeting and histone deacetylase (HDAC)/ cathepsin L (CTSL) responding functions in its molecular structure. A comprehensive set of surface-active evaluation revealed both polymer micelles had noteworthy activities in reducing surface tension, foaming, emulsification as well as solubilization. In the in vitro experiments, CUR@INPG micelles demonstrated superior anti-tumor activity and cellular uptake efficiency compared to free CUR and CUR@HDPG micelles, showing a preferential uptake by COX-2 positive cancer cells. As such, our investigation provided valuable insights into the potential applications of INPG in the pharmaceutical field.