Biomaterials have been popularly developed and applied in tissue engineering and biomedical science for human treatments due to their great interfacial compatibility with the biological environment. Simultaneously, profits from hydrogels’ 3D porous morphology, unique physical and mechanical properties, and remarkable biocompatibility and biodegradability, hydrogels have been widely researched in tissue engineering. Especially, the category of natural-derived hydrogels can offer higher biocompatibility, less toxicity and cytotoxicity, and lower immunogenicity due to their safe natural sources’ derivation. To better illustrate these points of view, this thesis reports four research on natural-derived hydrogels for tissue engineering applications. Four natural-derived hydrogels have been successfully developed: a poly(ethylene glycol) and α-cyclodextrin-based host-guest hydrogel, a gelatin and alginate-based Schiff’s base hydrogel, a lyophilized gelatin and polystyrene hydrogel-based hemostatic sealant, and a chitosan hydrogel-modified mussel-derived artificial tendon. All of these hydrogels have demonstrated significant effectiveness in biological assessments, addressing current challenges in tissue engineering. The host-guest hydrogel-based nanovaccine delivers therapeutic peptides in vivo and maintains sustained immunostimulations in malignant melanoma-bearing mice. The Schiff’s base hydrogel demonstrates significant potential in enhancing esophageal endoscopic submucosal dissection for early cancer adjuvant therapy. The lyophilized hemostatic hydrogel sealant exhibits promising hemostatic ability in traumatic brain injury mice models. Additionally, the chitosan-modified mussel-derived artificial tendon accelerates the tendon functional reconstruction at post-implantation in vivo assessment.