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Silanized cellulose derivatives represent a rapidly advancing class of biomaterials that combine the biocompatibility and sustainability of cellulose with the versatile reactivity of organosilanes to create high\u2010performance hydrogels. First developed in 2000 for bone and dental surgery, Si\u2010HPMC is recognized as a self\u2010hardening hydrogel, exhibiting a viscous liquid state at basic pH and a viscoelastic solid state at physiological pH. Since then, numerous studies have investigated Si\u2010HPMC hydrogels, consistently demonstrating their high biocompatibility, strong support for cell viability and proliferation, and functional barrier properties. These features make Si\u2010HPMC a versatile candidate for applications in tissue engineering and regenerative medicine. Furthermore, Si\u2010HPMC\u2010based biocomposites reinforced with nanoparticles, nanofibers, nanotubes, or ceramic particles have emerged as promising matrix hydrogels, combining enhanced mechanical resilience with improved bioactivity, particularly in cartilage, bone, and periodontal tissue engineering. This review highlights the pivotal role of Si\u2010HPMC hydrogels in advancing regenerative medicine, emphasizing their tunable mechanical and biological properties. 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