The objective of this study was to investigate the physicochemical, structural, and in vitro release properties of carboxymethyl cellulose (CMC)-based cryogel beads incorporating resveratrol-loaded microparticles (MP) for colon-targeted delivery system. CMC-based cryogel beads were produced by ionic cross-linking with different concentrations (2%, 3%, and 4%) of AlCl3. Based on FE-SEM images, CMC-based cryogel beads showed a smoother surface and more compact internal structure with increasing AlCl3 concentrations, which was proven to be due to the new cross-linking between the –COO− group of CMC and Al3+ by FT-IR analysis. The encapsulation efficiency of the cryogel beads was significantly increased from 79.48% to 85.74% by elevating the concentrations of AlCl3 from 2% to 4%, respectively. In vitro release study showed that all CMC-based cryogel beads had higher stability for resveratrol than MP in simulated gastric conditions and can efficiently deliver resveratrol to colon without the premature release.