Chronic Urticaria (CU) poses a significant therapeutic challenge, as conventional antihistamines are ineffective for about 40% of patients. This treatment gap is linked to key pathological drivers: impaired histamine metabolism due to low Diamine Oxidase (DAO) activity, immune dysregulation, and vitamin D deficiency. Addressing this need, our study evaluated NatureU Yan, a functional food designed to simultaneously target these pathways with active DAO, vitamin D, and Bifidobacterium longum BB536. In a 28-day trial involving 19 CU patients, this multi-targeted intervention led to striking clinical benefits. Patients exhibited a 170.71% improvement in disease control (UCT), an 80.82% reduction in symptom severity (UAS7), and an 88.24% enhancement in quality of life (DLQI), with an excellent safety profile. These findings position NatureU Yan as a promising, safe, and mechanistically grounded complementary option for CU management.