Cellulose nanofibers (CNF) are promising in composite functional materials, while the pulping and bleaching processes are usually needed in their production, leading to high cost and pollution. Here, a two-step liquid how water (LHW)/deep eutectic solvents (DES) pretreatment and wet mechanical grinding exfoliation strategy is employed to prepare CNF from three raw representative bulk lignocellulose materials (wheat straw, moso bamboo and poplar wood) without pulping and bleaching processes. CNF prepared from this universal approach exhibits desirable nanofibrous structure and good mechanical properties, which could serve as reinforcing and binding agents for the assembly of transition metal carbides (MXene) nanosheets to overcome their poor mechanical properties and structure stability. The obtained CNF/MXene composite film with closely stacked “mussel-like” structure exhibits enhanced mechanical properties, and demonstrates potential applications in electromagnetic interference shielding and electro-/photo-thermal heating. Furthermore, flexible and conductive CNF/MXene composite film could serve as dry electrodes to detect and monitor epidermal electrophysiological signals (electrocardiogram, electromyogram, etc.). This work provides a scalable and universal approach for the fabrication of high-performance CNF-based multifunctional materials, which is promising for the development of flexible and portable electronics.