The traditional treatment of colorectal cancer (CRC) involves a combination of chemotherapy and synthetic and natural drugs. In this study, a hybrid compound of 5-fluorouracil-curcumin encapsulated in bacterial nanocellulose (BNC) was evaluated for CRC treatment. Bacterial nanocellulose was produced using K. medellinensis and spray-dried. The encapsulation technique involved solvent evaporation. The interactions between cellulose and the hybrid were evaluated using adsorption isotherms and kinetics, and the system was morphologically and physiochemically characterized. The capsules were tested in vitro using Dukes' C and B CRC cells. The results indicated heterogeneous and incomplete adsorption of the hybrid onto the active sites of cellulose. Capsules with a BNC:hybrid mass ratio of 1:1 maintained the encapsulant properties while maximizing the drug load according to desorption in simulated stomach and colon fluids, where desorption in the colon was 1.79 times greater than that in the stomach. Finally, the cancer cell inhibition results indicated that the encapsulated hybrid performed better on Dukes' C-stage cells than on Duke's B-stage cells. In this study, a new system based on a hybrid cellulose compound was proposed for CRC treatment, specifically for metastatic CRC.