This study presents the synthesis and characterization of hexadecyl-modified SiO2 (HD-SiO2) nanoparticles and their application in the fabrication of a multilayered elastomer hybrid sheet to enhance water resistance in implantable biomedical devices. The surface modification of SiO2 nanoparticles was confirmed via FT-IR and TGA analyses, showing the successful grafting of hydrophobic hexadecyl groups. FE-SEM and DLS analyses revealed spherical HD-SiO2 nanoparticles with an average size of 360 nm. A multilayered elastomer hybrid sheet, consisting of a PDMS-based circuit-protecting body, a water resistance layer of HD-SiO2, a planarization layer, and a biocompatible layer of polydopamine, was fabricated and characterized. The water resistance layer exhibited superhydrophobic properties, with a water contact angle of 154.7° and a 27% reduction in water vapor transmission rate (WVTR) compared to the circuit-protecting body alone. The device packaged with both the circuit-protecting body and water resistance layer demonstrated a tenfold increase in operational lifespan in water medium compared to the device without the water resistance layer. Cytotoxicity and cell proliferation tests on human dermal fibroblast cells (HDFn) confirmed the biocompatibility of the multilayered sheet, with no significant cytotoxicity observed over 48 h.