Aqueous CdTe and organic CdSe/ZnS quantum dots (QDs) were encapsulated into SiO2 beads using various controlled sol-gel processes. Ligand exchange is a key to adjust the QD number in each bead and get a high photoluminescence (PL). Namely, partial ligand exchange from thioglycolic acid to 3-mercaptopropyotrimethoxysilane (MPS) on the CdTe QDs enables retention of the initial PL efficiency of the QDs in water, while the simultaneous addition of a poor solvent (ethanol) resulted in regulated assembly of the QDs through condensation of hydrolyzed MPS. SiO2 beads thus prepared had, for example, a diameter of 17 nm and contained 3 QDs each. The PL efficiency of these beads was 30%, while the initial PL efficiency was 38% in a colloidal solution. In addition, a method including surface silanization, phase transfer and self-assembly, and SiO2 shell growth has been developed to incorporate multiple hydrophobic CdSe/ZnS QDs into SiO2 beads where they are well suited for bio-application due to their high brightness, less-cytotoxic, and non-blinking nature. To investigate the potential use for labeling in bio-applications, SiO2 beads with multiple QDs were conjugated with IgG using streptavidin-maleimide as linkers. This preparation method is an important step towards fabricating intensely emitting biocompatible SiO2 beads impregnated with semiconductor QDs.