We have probed the local atomic structure of the interface between a CdSe quantum dot (QD) and a sodium silicate glass matrix. Using ab initio molecular dynamics simulations, we determined the structural properties and bond lengths, in excellent agreement with previous experimental observations. On the basis of an analysis of radial distribution functions, coordination environment, and ring structures, we demonstrate that an important structural reconstruction occurs at the interface between the CdSe QD and the glass matrix. The incorporation of the CdSe QD disrupts the Na–O bonds, while stronger SiO4 tetrahedra are reformed. The existence of the glass matrix breaks the stable 4-membered (4MR) and 6-membered (6MR) Cd–Se rings, and we observe a disassociated Cd atom migrated in the glass matrix. Besides, the formation of Se–Na and Cd–O linkages is observed at the CdSe QD/glass interface. These results significantly extend our understanding of the interfacial structure of CdSe QD-doped glasses and provide physical and chemical insight into the possible defect structure origin of CdSe QD, of interest to the fabrication of the highly luminescent CdSe QD-doped glasses.