Cellulose nanofibers (CNFs) are of interest for use as bio-based reinforcement, in view of their superior mechanical properties and large aspect ratio and surface area. However, these highly fibrillated, flexible and hydrophilic fibers tend to entangle and form agglomerates, especially within hydrophobic matrices. Considering the attractive properties of CNFs, the focus of this investigation has been to explore their potential use to enhance the properties of two thermoplastics, i.e., bio-based/biodegradable (hydrophobic) polylactide (PLA) and poly(ethylene oxide) (PEO), a hydrophilic and biodegradable/biocompatible polymer. Initially, PLA/CNF and PEO/CNF biocomposites were prepared separately via solution methods, and the effects of CNFs on some critical properties of each matrix were investigated. Subsequently, the compatibilization effects of poly(ethylene glycol) (PEG), a low molecular weight PEO, on the dispersion/distribution of the CNFs within the PLA matrix and on the rheological and mechanical properties of PLA/CNF biocomposites were examined. Scanning electron microscopy confirmed that the CNFs were well dispersed in the PLA and PEO matrices. Moreover, improved dispersion/distribution of nanofibers in PLA was achieved using PEG as compatibilizer. The complex viscosity and storage modulus of PLA and PEO increased substantially by incorporating CNFs. In the case of PLA/CNF composites, the increases were one order of magnitude larger when a PEG/CNF masterbatch was used. The storage modulus of the PLA/PEG/2 wt% CNF/ biocomposite measured in dynamic mechanical thermal analysis (DMTA) at room temperature and 80 °C, increased by 42 and 553%, respectively, relative to the neat PLA. All biocomposite films showed good light transmittance. These results demonstrate that, using proper preparation methods, CNFs can improve the properties of both hydrophilic and hydrophobic matrices at very low contents.