<p>This study investigated a novel approach for producing gellan gum (GG)-based cryogel beads containing piperine-loaded chitosan (CS) microparticles as a delivery system for piperine. The cryogel beads were fabricated using different GG concentrations (0.5%, 1.0%, 1.5%, and 2.0%) in the presence of an ionic crosslinker (Ca²⁺). The electrostatic interactions between CS and GG, ionic crosslinking between GG and calcium ions, and the enhancement of hydrogen bonding were confirmed by Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction analyses. Gaussian multi-peak fitting of FTIR spectra revealed that the increase in GG content promoted the formation of intermolecular hydrogen bonds (mainly OH···O) during freeze-thaw process, with their relative contribution increasing from 47.3% to 54.9%. Scanning electron microscopy analysis showed that increasing GG concentration resulted in a denser cryogel network with smaller pores. Accordingly, the encapsulation efficiency of piperine increased from 37.8% to 74.2% as the GG concentration increased from 0.5% to 2.0%. All GG-based cryogel beads effectively suppressed piperine release in simulated gastric and intestinal fluids, with the lowest release (7.4% in simulated gastric fluid and 4.5% in simulated intestinal fluid) observed for beads prepared with 2.0% GG. In addition, these beads provided the highest protection against piperine degradation, exhibiting an 89.6% piperine retention rate after 7 days of storage at 4&#xa0;°C. Overall, the results demonstrate that GG-based cryogel beads, particularly those prepared with 2.0% GG, are effective encapsulating matrices for piperine-loaded CS microparticles and show potential as a colon-targeted delivery system by preventing premature release in the upper gastrointestinal tract.</p>