Hydrogels are one of the important biomaterials for tissue engineering applications. The hydrogel scaffolds’ state-of-the-art properties for clinical applications are subject to on-going researches. Hydrogels, such as hybrid and protein-based ones, contain protein domains. Hydrogels show unique advantages compared to other polymeric materials; which made them applicable as periodontal materials and drug carriers, as well as bone matrices. The first description of its use was developed by a Scottish chemist, Thomas Graham, as a solid, jelly-like material that can have different physical and mechanical properties. Gels are defined as a substantially dilute crosslinked system, which doesn’t have flow in the steady-state. Gels can be typically characterized as liquids, while they behave like solids due to a 3D cross-linked network within the liquid. The gels’ IUPAC definition classifies them as a non-fluid polymer network that is expanded throughout its whole volume by a fluid. Thus, this chapter aims to describe the composition, synthesis techniques, and applications of hydrogel scaffolds for biomedical approaches.