CD4⁺ T helper (Th) cells are a crucial player in host defense but under certain conditions can contribute to the pathogenesis of inflammatory and autoimmune diseases. Beside the Th1/Th2 subset, several additional Th subsets have been identified, each with a distinctive transcription factor, functional properties, signature cytokine profile, and possible role in the pathophysiology of diseases. These newer Th subsets include Th17, regulatory Th cells (Tregs), and more recently, Th9, Th22, and follicular T helper cells. Interestingly, imbalance of Th subsets contributes to the immunopathology of several disease states. Therefore, targeting the imbalance of Th subsets and their signature cytokine profiles by a safe, effective and inexpensive nutraceutical agent such as curcumin could be helpful to treat autoimmune and inflammatory diseases. In this study different Th subsets and how the imbalance of these subsets could promote pathology of several diseases has been reviewed. Furthermore, the role of curcumin in this process will be discussed and the impact of targeting Th subsets by curcumin.