As one of the most important barriers in the body, the intestinal barrier is a key factor in maintaining human health. Ageing of the intestine is a degenerative process that is closely associated with a variety of poor health conditions in the elderly. Inflammation and the immune system are anti-ageing targets that can regulate the function of the intestine. Nucleotides (NTs) are involved in important physiological and biochemical reactions in the body, but there are few studies about their effect on the ageing intestine. This paper examines the role of exogenous NTs in the ageing intestine. For this purpose, we used senescence-accelerated mouse prone-8 (SAMP8) mice and senescence-accelerated mouse resistant 1 (SAMR1) mice for the experiment, and randomly divided the mice into NTs-free, Normal Control, NTs-low, NTs-medium, NTs-high, and SAMR1 groups. After 9 months of intervention, we collected the colon tissue of mice for testing. In our study, exogenous NTs could increase bodyweight of mice during ageing and improve the morphological structure of the intestine, and we found that NTs could promote the secretion of intestinal protective factors, such as TFF3 and TE. Furthermore, supplementation with NTs suppressed intestinal inflammation and improved intestinal immunity, possibly by activating the p38 signaling pathway. These results suggest that exogenous NTs are able to maintain the health condition of the ageing intestine.