Gelatin methacryloyl (GelMA) hydrogels are widely used for tissue regeneration. Nonetheless, a pure GelMA hydrogel cannot efficiently serve for cartilage regeneration because of weak mechanical properties and brittleness. In this study, we established a mussel-inspired strategy for tuning the mechanical properties of GelMA hydrogels by intercalating oligomers of dopamine methacrylate (ODMA) into the chain of GelMA. After the ODMA intercalated, the hydrogel became tough and resilient. This is because ODMA intercalation reduces the high density of entangled GelMA chains and introduces additional sacrificial physical cross-linking into the hydrogel. Rheological analysis showed that the ODMA-GelMA hydrogel was mechanically stable at body temperature. The hydrogel also manifested a sustained protein release because of the ODMA catechol groups. Furthermore, the ODMA-GelMA hydrogel was found to have good biocompatibility and affinity for cells and tissues because of the catechol groups on ODMA. In vitro, the hydrogel promoted mesenchymal stem cell adhesion and growth, and in vivo, it promoted cartilage regeneration after loading with chondroitin sulfate or TGF-β3. The hydrogel can serve as a growth-factor-free scaffold for cartilage regeneration. This hydrogel not only provided a favorable microenvironment for cartilage repair but also could serve as a promising candidate material for repair of other tissues. This mussel-inspired strategy of introduction of reactive oligomers instead of polymers into a brittle hydrogel network may be extended to the development of other tough hydrogels for biomedical applications.