In recent years, hydrogels as drug carriers have been receiving great interest due to their ability to change their behavior in response to one or more external stimuli. However, their initial burst release profile limits their practical applications. Therefore, we prepared a bio-based hydrogel nanocomposite (HNC) using starch, itaconic acid, acrylic acid and gelatin in the presence of CNF/ZnO-based nanohybrid (ZONH) and used it to evaluate the pH-sensitive drug release properties in different pH solutions. The prepared HNCs were analyzed using various spectroscopic and microscopic techniques. The BET analysis and swelling test of the HNC indicated improved porosity and swelling capacity due to the addition of ZONH. From the drug release study, sustained drug release rate was observed at pH 4 than those at pH 7.4 and 9, indicating controlled release as well as pH responsive behavior of the HNC. Moreover, the drug released HNC was reused as a photocatalyst for dye degradation and achieved good degradation (%). The antibacterial activity of ZONH and HNC was observed against EC and SA bacterial strains from the antibacterial test. In summary, the prepared HNC can be considered as a potential sustainable DDS for biomedical applications as well as a photocatalyst for dye contaminated water treatment.