Abstract: Sol-gel-derived xerogels are good support matrices for chemical and biological sensing elements. The development of stable and optimal sensing platforms is predicated on the detailed understanding of the behavior of the immobilized recognition elements within the host matrices. Luminescence spectroscopy has proven to be a good choice for the characterization of the local microenvironment within host platforms and the dynamics of the probe-labeled proteins within xerogel-based nanocomposites. This dissertation centers on establishing systematic methods to characterize and tailor the performance of xerogel-based sensing platforms. The work is divided into two parts. First, we investigated the analytical figures of merit (e.g., sensitivity, linearity of calibration curves and stability) of pin-printed or spin cast O₂-responsive sensing arrays and films. The origin of the changes in sensor sensitivity was explored and the observed sensor performances were correlated to the physicochemical properties of the platform compositions. Second, we characterized the behavior of acrylodan-labeled PEGylated human serum albumin (PEGylated-HSA-Ac) in buffer and within xerogel monoliths. Thermodynamic parameters were calculated based on the protein unfolding curves (chemical and thermal denaturation). The effects of covalent attachment of PEG and the organic groups within ORMOSIL-based xerogels on the emission spectra and the time-dependent spectral relaxation were discussed.