Currently, the development of innovative materials for the treatment of various diseases is highly interesting and effective. Additionally, in recent years, environmental changes, including the search for a sustainable world, have become the main goal behind developing sustainable and suitable materials. In this context, this research produced innovative hydrogels that incorporate cellulose nanocrystals and nanofibres from underutilised fibres from a semiarid region of Brazil; the hydrogels were loaded with vitamin D to evaluate controlled drug release for the treatment of diverse diseases. Spectroscopic (FTIR, Raman, UV−VIS), X-ray diffraction, zeta potential and morphology (SEM, TEM) analyses were used to characterise these hydrogels. In addition, biocompatibility was assessed using a resazurin assay, and the in vitro kinetic accumulative release of vitamin D was measured. The results showed that nanocrystals and nanofibres changed the structure and crystallinity of the hydrogels. In addition, the chemical groups of the hydrogels were red- and blueshifted in the FTIR spectra when the nanocrystals, nanofibres and vitamin D were incorporated. Moreover, the nanocrystals and nanofibres were homogeneously spread into the hydrogel when vitamin D was loaded into the hydrogel matrix. Furthermore, the cytotoxicity was greater than 90%. Additionally, the in vitro accumulative kinetic data of vitamin D release were robust (close to 40 ng·mL−1), with equilibrium being reached in the first 30 min. These results confirm the potential of using these hydrogels as therapeutic biomaterials for diverse diseases and problems in humans, mainly in women, who are the most harmed by vitamin D deficiency.