The sol-gel encapsulation of labile biological materials with catalytic and recognition functions within robust polymer matrices remains a challenging task, despite the considerable research that has been focused on this field. Herein, we describe a new class of precursors, based around polyol silicates and polyol siloxanes, especially those derived from glycerol, that addresses problems faced with traditional bioencapsulation protocols. Poly(glyceryl silicate) (PGS) was prepared and employed for sol-gel bioentrapment, in an approach distinguished by a high biocompatibility and mild encapsulation conditions, and which enables the reproducible and efficient confinement of proteins and cells inside silica. The methodology was extended to metallosilicate, alkylsiloxane, functionalized siloxane, and composite sol-gels, thereby allowing the fabrication of a physicochemically diverse range of bio-doped polymers. The hybrid materials display activities approaching those of the free biologicals, together with the high stabilities and robustness that characterize sol-gel bioceramics. Indeed, the bioencapsulates performed better than those fabricated from tetramethoxysilane, poly (methyl silicate) or alcohol-free poly(silicic acid), even when the latter were doped with glycerol. The activity enhancements appear to derive at least in part from the unusual microstructure of PGS sol-gels, in particular their high porosity, although the underlying mechanisms are unclear. Differences in precursor hydrolysis/condensation, development of gel structure, biological-matrix interactions, precursor toxicity, and pore collapse probably all contribute to the observed efficiency of the PGS materials. The performances of the encapsulates are compared with conventional sol-biogels and other immobilizates, in representative biocatalyst, biosensor, and biodiagnostic applications.