Background/Objectives: Psoriasis vulgaris is a chronic inflammatory skin condition with significant psychosocial burden. While phototherapy remains one of the most widely used treatment regimens, novel modalities like blue light therapy offer UV-free alternatives with potentially more favorable safety profiles, but their systemic immunomodulatory effects remain poorly understood. We aimed to evaluate the impact of full-body blue light irradiation on clinical outcomes and selected systemic biochemical and immunological markers in patients with mild-to-moderate psoriasis vulgaris. Methods: This preliminary study involved 21 patients (13 females, 8 males) with mild-to-moderate psoriasis vulgaris. Participants received ten sessions of full-body blue light therapy (453 nm, 40 mW/cm², 30 min per session). Clinical assessments (PASI, PGA, DLQI, VAS, Pruritus Scale) and serum analyses of inflammatory (TNF-α, IL-13, IL-17, IL-31), metabolic (adiponectin, 25(OH)D3), and neuroimmune markers (serotonin, kynurenic acid, quinolinic acid) were performed pre- and post-treatment. Results: Significant improvements were observed in PASI, PGA, DLQI, and pruritus scores (p < 0.05). 25(OH)D3, serotonin, and kynurenic acid levels increased significantly, while IL-31 and IL-17 levels decreased and IL-13 levels increased; TNF-α, adiponectin, and quinolinic acid levels showed no significant changes. Counterintuitively, correlation analysis demonstrated a moderate positive association between changes in IL-13 and PASI improvement (r = 0.51, p = 0.02), while changes in other biochemical parameters were not significantly associated with clinical outcomes. Conclusions: Full-body blue light therapy resulted in significant clinical improvement accompanied by heterogeneous systemic immunometabolic changes. These findings suggest complex, pathway-specific immunomodulation, but this requires further investigation in larger controlled studies.