The metabolic heterogeneity of immune cells provide an opportunity for different immune cells to differentiate into effector or regulatory cells. Targeting the metabolism of immune cells with metabolic inhibitors is a new approach in immunosuppression. Therefore, selective inhibition of basic metabolic pathways, which are necessary for all healthy cell survival, can still show selectivity toward immune cells. It all depends on the degree of reliance on immune cells on those pathways. The delicately balanced interplay between protective immunity and inflammatory conditions is critical for the activation/differentiation of various immune cells. On encounter with antigen and receiving appropriate co-stimulatory signals, naïve T cells activate downstream metabolic reprogramming for rapid cell growth and proliferation to fuel their specific effector functions. Immunometabolism provides a greater room for a therapeutic window in transplantation settings and autoimmune disease treatment. Furthermore, LKB1 is an important upstream kinase that strengthen the stability of Tregs, and their signaling can be co-regulated to enhance the stability of Tregs. Notably, LKB1 is a metabolic regulator that connects cellular metabolism to immune cell functions. Recent work has demonstrated that modulating Treg function by targeting metabolic pathways and LKB1 signaling in models of transplantation and inflammatory diseases do not cause any visible toxicity, which advocates this strategy as a new therapeutic intervention for treating inflammatory diseases.