Cellulose nanofibrils (CNF) are mixed with plasticizers; sorbitol and glycerol, through high-pressure homogenization to prepare multifunctional biohybrid films. The resulting plasticized films obtained after solvent evaporation are strong, flexible and demonstrate superior toughness and optical transparency. The oxygen barrier properties of the biohybrid films outperform commercial packaging materials. The sorbitol-plasticized CNF films possess excellent oxygen barrier properties, 0.34 cm3·μm/m2·day·kPa at 50 % relative humidity, while significantly enhancing the toughness and fracture strength of the films. CNF films plasticized by 20 wt.% of sorbitol and glycerol could before rupture, be strained to about 9 % and 12 %, respectively. The toughness of the plasticized films increased by ca. 300 % compared to the pristine CNF film. Furthermore, the water vapor barrier properties of the biohybrid films were also preserved by the addition of sorbitol. CNF films plasticized with sorbitol was demonstrated to simultaneously enhance fracture toughness, work of fracture, softening behavior while preserving gas barrier properties. Highly favorable thermomechanical characteristics were found with CNF/sorbitol combinations and motivate further work on this material system, for instance as a thermoformable matrix in biocomposite materials. The unique combination of excellent oxygen barrier behavior, formability and optical transparency suggest the potential of these CNF-based films as an alternative in flexible packaging of oxygen sensitive devices like thin-film transistors or organic light-emitting diode displays, gas storage applications and as barrier coatings/laminations in packaging applications, including free-standing films as aluminium-replacement in liquid board and primary packaging, as replacement for polyethylene (PE) in wrapping paper, e. g. sweats and confectionary.