The research on vitreous substitutes aims to find materials that can replace the functions of natural vitreous and be used to treat vitreoretinal diseases. Traditional substitutes such as gases and silicone oil have many drawbacks. However, hydrogels are regarded as highly potential substitutes due to their high water content, good biocompatibility, adjustable physical and chemical properties, and potential for controlled drug release. Researchers have developed two types of in-situ cross-linked hydrogels: chemical cross-linking and physical cross-linking. Chemical cross-linked hydrogels achieve in-situ gelation by forming chemical covalent bonds, showing good stability and degradability, but still require precise control of the degradation rate and the safety of degradation products. Physical cross-linked hydrogels utilize physical or supramolecular interactions between polymer chains to achieve in-situ gelation, having low toxicity and self-repairing properties, but they degrade too quickly and require a combination of physical and chemical cross-linking to extend the material's retention time. Additionally, researchers have explored in-situ cross-linked hydrogels loaded with anti-inflammatory, antioxidant, or anti-proliferative drugs for vitreoretinal disease, elevating vitreous substitutes from simple physical filling to an active treatment level. Future research needs to further optimize the comprehensive performance of hydrogels and deeply study their long-term biological activity impact on the intraocular microenvironment to promote their clinical translation.