Aspirin is one of the most commonly prescribed medications. Evidence shows that it can even treat and prevent intestinal tumors. However, it has also caused a great deal of controversy due to its intestinal side effects. We therefore explored whether aspirin was beneficial or harmful to the intestines. We used aspirin continuously interfered with C57BL/6 J mice for 48 weeks, examining their intestinal tissues at 13, 26 and 48 weeks to determine the drug’s effect on the intestines. In addition, we used flow cytometry (FCM) used to detect T cells and expression of T-cell immunoreceptor with immunoglobulin (Ig)– and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) on their surfaces to determine aspirin’s immunomodulatory effects. The results showed that long-term aspirin intervention could reverse damage to the intestines, an effect related to the drug’s significant inhibitory effect on TIGIT. The change in TIGIT level could regulate T-cell subsets, so that counts of Cluster of Differentiation 4 (CD4)⁺/chemokine (C-X3-C motif) receptor 3 (CXCR3)⁺ T-helper 1 (T_h1) cells and CD4⁺/interleukin-4 (IL-4)⁺ T_h2 cells increased, while those of CD4⁺/C-C chemokine receptor type 6 (CCR6)⁺ T_h17 cells and CD4⁺/CD25⁺ regulatory T cells (Tregs) decreased. In summary, we demonstrated that long-term aspirin intervention could inhibit TIGIT, regulating T cells to reverse damage to the intestines. Furthermore, aspirin is a potential therapy for diseases related to an increase in TIGIT.