TRPV1 is a Ca²⁺-permeable channel studied mostly as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here we found that TRPV1 was functionally expressed in CD4⁺ T cells, where it acted as a non–store-operated Ca²⁺ channel and contributed to T cell antigen receptor (TCR)-induced Ca²⁺ influx, TCR signaling and T cell activation. In models of T cell–mediated colitis, TRPV1 promoted colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4⁺ T cells recapitulated the phenotype of mouse Trpv1^−/− CD4⁺ T cells. Our findings suggest that inhibition of TRPV1 could represent a new therapeutic strategy for restraining proinflammatory T cell responses.