Cellulose nanofibrils (CNFs) have attracted attention as building blocks for sustainable materials owing to their high performance and the advantages of their abundant natural resources. Bioinspired CNF/polymer nanocomposites, consisting of a soft polymer phase and a high fraction (>50 wt %) of CNF reinforcement, have been focused on excellent mechanical properties, including Young's modulus, mechanical strength, and toughness, mimicking the energy dissipation system in nature. However, efficient softening and toughening with a small amount of the soft phase is still a challenge because a large amount of the polymer phase (nearly 50%) is still required to provide ductility and toughness. Here, we describe a topological strategy in the polymer phase for efficient toughening of bioinspired CNF nanocomposites with a water-soluble comb polyurethane (PU). The comb PU provided higher elongation at break and more efficient flexibility for the nanocomposite than the linear PU, even at a small content. Moreover, CNF nanocomposites with 30 wt % of PU content and tetrabutylammonium as bulky counterions showed enhanced toughness (180% higher) and strain at break (250% higher) when compared to pure CNF due to the promotion of slippage between nanofibrils. Scanning electron microscopy (SEM) images of the fracture surface for CNF/comb PU nanocomposites displayed the pull-out of mesoscale layers and nanofibrils, supporting that the comb topology promotes the slippage between fibrils. Furthermore, the rheological study revealed that the comb PU has an entanglement plateau modulus lower than linear PU by 1 order of magnitude, related to the loosened entanglements. Our study establishes an efficient softening and toughening strategy while using small amounts of polymer phase addition, promoting interfibrillar slippage with the loosely entangled comb PU phase.