Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation where CD4(+) T lymphocytes play an essential role. Accumulating evidence suggests that immune responses driven by CD4(+) T cells are critically regulated by various metabolic pathways including oxidative phosphorylation and glycolysis. Here we show that CARS2/CPERS-dependent supersulfide metabolism restrains CD4(+) T cell proliferation in a cell-intrinsic manner. Under steady state, Cars2 (+/-) mice exhibited spontaneous accumulation of effector/memory CD4(+) T cells in the colon with age. In lymphopenic conditions, Cars2 (+/-) CD4(+) T cells showed enhanced cell cycle entry with reduced expression of a cell cycle inhibitor Trp53 and triggered an exacerbated form of colitis, the response being rescued by treatment with a supersulfide donor glutathione trisulfide (GSSSG). Furthermore, re-analysis of publicly available gene datasets of human colonic CD4(+) T lymphocytes revealed that downregulation of CARS2 was associated with pathogenesis of IBD, and indeed, addition of GSSSG inhibited human CD4(+) T cell proliferation in vitro. Together these observations reveal that CARS2/CPERS-dependent supersulfide metabolism is essential for homeostasis of intestinal effector/memory CD4(+) T cells, and further suggest that dysregulation of the same metabolic pathway can lead to development of gut inflammation both in mice and humans.