Response surface methodology was employed to investigate the effects of common food and digestive tract conditions (pH, temperature, sodium chloride) on the adsorption of polyphenols to cellulose. Major dietary polyphenols selectively bound to cellulose to different extents and exhibited different binding behaviour changes with the environment. Three factors were studied, of which pH (3–7) was found to be the most influential factor, followed by temperature (4–37 °C), while NaCl (0–100 mM) had no significant effect on polyphenol adsorption. Polyphenol adsorption was sensitive to variation in physicochemical parameters: cyanidin-3-glucoside > ferulic acid > (+/
)-catechin. Second-order polynomial equation was a significant and adequate model to express the interaction relationships between polyphenol adsorption and changes in the binding conditions, as the experimental test values agreed with predicted adsorption values under optimised binding conditions. These findings contribute to knowledge on the mechanism of polyphenol–cellulose interactions, important for both food quality and nutritional value.