To study the effect of diet supplementation with polyphenols on several functions suffering age-related changes, in peritoneal leucocytes from mature and old mice. Five groups of female ICR mice were used. Four groups received a supplementation (20% wt/wt) of biscuits with different cereal fractions naturally rich in polyphenols (named CO49, CO50, CO52, CO53), containing different amounts of catechin, p-hydroxybenzoic acid, vanillic acid, p-coumaric acid, sinapic acid, ferulic acid, rutin and oryzanol. The control group received only standard maintenance diet. Peritoneal suspensions were obtained after 15 and 30 weeks of diet supplementation, when the age of the animals was 49 ± 2 (mature mice) and 64 ± 2 weeks (old mice), respectively. The functions analysed were: chemotaxis of macrophages and lymphocytes, phagocytosis of particles by macrophages, intracellular superoxide anion levels, lymphoproliferative response to mitogens (concanavalin A and lipopolysaccharide), interleukin-2 secretion and natural killer (NK) activity, as functions that decrease with age, and adherence of macrophages and lymphocytes and tumour necrosis factor-α secretion as functions with age-related increase. The supplementation, in general, increased the functions that decrease with age and decreased those that increase with age. There were differences in the effects shown by the four kinds of biscuits depending on the function studied and the number of weeks of supplementation. Since the immune system has been proposed as a good marker of health and predictor of longevity, diet supplementation with cereals naturally rich in polyphenols could be an important way for health preservation with age and reaching high longevity.