<p>Long-term controlled release in drug-loaded injectable hydrogels is challenging in the injection-based treatments of ocular diseases. Herein, injectable hyaluronic acid (HA)-based hydrogels were synthesized in situ via Schiff base reaction between amino-functionalized hyaluronic acid (NHA) and three aldehyde-functionalized β-cyclodextrin (β-CD) derivatives: aldehyde β-cyclodextrin (ACD), aldehyde linear poly-β-cyclodextrin (ALCD), and aldehyde branched poly-β-cyclodextrin (ABCD). The composition, structure, and properties of the prepared hydrogels were analyzed using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and dynamic rheometry. The hydrogels exhibited a pore size range of 50–250 μm, a swelling degree of 27.1–45.0%, and a gelation time of 60–300 s, demonstrating suitable microstructural and rheological properties for clinical applications. By leveraging the dual functionality of the aldehyde β-CD derivatives as both crosslinking agents and drug carriers (Voriconazole (VCZ) was as a model drug), the hydrogels achieved long-term controlled release (&gt; 60 days) with quasi-zero-order kinetics in the later stage, alongside excellent cellular compatibility, particularly for NHA/ACD (R² = 0.99701) and NHA/ABCD (R² = 0.98931). This study presents the first comparative analysis of the effects of structurally distinct aldehyde β-CD/poly-β-CD derivatives on hydrogel properties. The findings provide novel insights into the structural design of aldehyde-functionalized β-CD derivatives for the development of long-term controlled release injectable hydrogels in about 30–60 days as well as tuned. Simultaneously, the corresponding <i>in vivo</i> animal safety and efficacy experiments could further validate the practical application potential of this gel platform in the future work. Conclusively, the injectable HA-based hydrogels have potential as promising candidates for treating chronic ocular pathologies requiring long-term therapy.</p> Graphical Abstract <p></p>