The balance between the immune system and its metabolism is becoming an effective therapeutic alternative in various inflammatory diseases, including organ transplantation. The interaction between the immune and metabolic pathways play a critical role in dictating disease pathology and progression, and the differences in the bioenergetic demands between immune cells enable them to differentiate into effector and regulatory cells. Recent studies have suggested that changes in intracellular metabolic programs control T cell activation, proliferation and differentiation into T effector (Teffs) or T regulatory cells (Tregs), and metabolic differences between Tregs and Teffs can shift the balance toward a more specific immune tolerance in organ rejection. Pharmacological targeting of T cells metabolism affects the balance between effector and regulatory function of T cells.This therapeutic modulation are of great interest in cancer, autoimmunity, and organ transplantation. In this review, we discuss major metabolic pathways that influence the activation, proliferation and differentiation of Tregs, and also special emphasis on liver kinase B1 (LKB1) pathway that provide stability of Tregs. We also highlight how Tregs metabolic regulome and LKB1 signaling pathway relationship contribute to rescue organ transplants from associated injuries and chronic rejection.