Activated T cells are pathological in various autoimmune and inflammatory diseases including Psoriasis, and also in graft rejection and graft‐versus‐host‐disease. In these pathological conditions, selective silencing of activated T cells through physiological receptors they express remains a clinical challenge. In our previous studies we found that activation of dopamine receptors (DRs) in resting human T cells activates these cells, and induces by itself many beneficial T cell functions. In this study, we found that normal human T cells express all types of DRs, and that expression of D1R, D4R and D5R increases profoundly after T cell receptor (TCR) activation. Interestingly, DR agonists shift the membrane potential (Vm) of both resting and activated human T cells, and induces instantaneous T cell depolarization within 15 seconds only. Thus, activation of DRs in T cells depolarize these immune cells, alike activation of DRs in neural cells. The skin of Psoriasis patients contains 20‐fold more D1R+ T cells than healthy human skin. In line with that, 25‐fold more D1R+ T cells are present in Psoriasis humanized mouse model. Highly selective D1‐like receptor agonists, primarily Fenoldopam (Corlopam) – a D1‐like receptor agonist and a drug used in hypertension, induced the following suppressive effects on activated T cells of Psoriasis patients: reduced chemotactic migration towards the chemokine SDF‐1/CXCL12; reduced dramatically the secretion of eight cytokines: tumor necrosis factor‐α, interferon‐γ, interleukin‐1β (IL‐1β), IL‐2, IL‐4, IL‐6, IL‐8 and IL‐10; and reduced three T cell activation proteins/markers: CD69, CD28 and IL‐2. Next, we invented a novel topical/dermal Fenoldopam formulation, allowing it to be spread on, and providing prolonged and regulated release in, diseased skin. Our novel topical/dermal Fenoldopam: reduced secretion of the eight cytokines by activated human T cells; reduced IL‐1β and IL‐6 secretion by human lipopolysaccharide‐inflamed skin; eliminated preferentially >90% of live and large/proliferating human T cells. Together, our findings show for the first time that both resting and activated T cells are depolarized instantaneously via DRs, and that targeting D1‐like receptors in activated T cells and inflamed human skin by Fenoldopam, in Psoriasis, and potentially in other T cell‐mediated diseases, could be therapeutic. Validation in vivo is required.