Great advancements have been made in understanding the pathogenesis of SS, but there remain unmet needs for effective and targeted treatments. Glandular and extraglandular dysfunction in SS is associated with autoimmune lymphocytic infiltration that invades the epithelial structures of affected organs. Regulatory T (Treg) cells are a subset of CD4+ T lymphocytes that maintain self-tolerance during physiological conditions. Besides inhibiting excessive inflammation and autoimmune response by targeting various immune cell subsets and tissues, Treg cells have also been shown to promote tissue repair and regeneration in pathogenic milieus. The changes of quantity and function of Treg cells in various autoimmune and chronic inflammatory disorders have been reported, owing to their effects on immune regulation. Here we summarize the recent findings from murine models and clinical data about the dysfunction of Treg cells in SS pathogenesis and discuss the therapeutic strategies of direct or indirect targeting of Treg cells in SS. Understanding the current knowledge of Treg cells in the development of SS will be important to elucidate disease pathogenesis and may guide research for successful therapeutic intervention in this disease.