Cellulose-based composite macrogels made by cellulose fiber/cellulose nanofiber (CCNM) were used as an intestine delivery vehicle for probiotics. Cellulose nanofiber (CNF) was prepared by a 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation system, and the carboxyl groups in CNF acted as pore size and pH responsibility regulators in CCNMs to regulate the probiotics loading and controlled release property. The macrogel presented a porosity of 92.68% with a CNF content of 90%, and the corresponding released viable Lactobacillus plantarum (L. plantarum) was up to 2.68 × 108 cfu/mL. The porous structure and high porosity benefited L. plantarum cells to infiltrate into the core of macrogels. In addition, the macrogels made with high contents of CNF showed sustainable release of L. plantarum cells and delivered enough viable cells to the desired region of intestine tracts. The porous cellulose macrogels prepared by a green and environmental friendly method show potential in the application of fabricating targeted delivery vehicles of bioactive agents.