Efficient wound healing is feasible when the dressing materials simultaneously target multiple factors causing wound chronicity, such as deleterious proteolytic and oxidative enzymes and bacterial infection. Herein, entirely bio-based multifunctional self-assembled hydrogels for wound healing were developed by simply mixing two biopolymers, thiolated hyaluronic acid (HA-SH) and silk fibroin (SF), with lignin-based nanoparticles (NPs) as both structural and functional elements. Sono-enzymatic lignin modification with natural phenolic compounds results in antibacterial and antioxidant phenolated lignin nanoparticles (PLN) capable of establishing multiple interactions with both polymers. These strong and dynamic polymer-NP interactions endow the hydrogels with self-healing and shear-thinning properties, and pH-responsive NP release is triggered at neutral to alkaline pH (7–9). Despite being a physically crosslinked hydrogel, the material was stable for at least 7 days, and its mechanical and functional properties can be tuned depending on the polymer and NP concentration. Furthermore, human skin cells in contact with the nanocomposite hydrogels for 7 days showed more than 93% viability, while the viability of clinically relevant Staphylococcus aureus and Pseudomonas aeruginosa was reduced by 99.7 and 99.0%, respectively. The hydrogels inhibited up to 52% of the activity of myeloperoxidase and matrix metalloproteinases, responsible for wound chronicity, and showed a strong antioxidant effect, which are crucial features promoting wound healing.