Polymer-gold nanoparticle nanocomposites based on POSS polymer with a thiol group was obtained by laser ablation in liquids (LAL). Laser ablation of a gold target in a solution of ethanol and POSS-thiol produced high purity nanocomposites of POSS decorated with gold nanoparticles (Au NPs) in colloidal suspension. TEM characterization showed spherical geometry of the Au NPs, mainly smaller than 60 nm. The UV–Vis-NIR spectroscopy exhibited the typical absorbance spectra for spherical Au NPs in the visible range (520–550 nm) related to plasmonic behavior. POSS-Au NPs nanocomposites exhibited an improvement in the colloid stability, absorbance peak and reproducibility, compared to the NPs without POSS-thiol. The optimal values were found for Au NPs synthesized in a POSS-thiol ethanol solution at 0.0168 mM. The low cytotoxic activity in human gingival fibroblasts (HGF) suggest the biocompatibility of the nanocomposite. The optical properties and biocompatibility of the nanocomposite shows its use viability for applications as biosensors based in optical response.