Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder frequently associated with dysregulated Th1/Th2 immune balance and impaired regulatory T (Treg) activity. Although conventional treatments can reduce clinical symptoms, concerns regarding long-term adverse effects have led to increased interest in complementary and functional dietary materials with immunomodulatory potential. Bioprocessed black rice bran (BRB-F) and balloon flower root fractions (BFR-F) have individually demonstrated anti-inflammatory activities, but their combined oral efficacy and mechanisms in AD remain insufficiently characterized. Methods Mechanistic in vitro assays were first performed using a human B-cell line to measure IgE secretion, mouse and/or human mast cells to evaluate degranulation and TSLP release, and keratinocyte cultures to quantify TARC, MDC, and IL-6 production. These assays were used to determine whether BRB-F and BFR-F individually or cooperatively modulate immune and epithelial cell activation relevant to AD pathology. Subsequently, an AD-like phenotype was induced in BALB/c mice by topical application of 1-chloro-2,4-dinitrobenzene followed by mite extract. Animals received dietary supplementation with a 3:1 BRB-F:BFR-F mixture (10–80 mg/kg/day), and clinical skin inflammation, ear histopathology, and cytokine profiles were analyzed to assess Th1/Th2 balance and Treg-associated markers. Results Dietary supplementation with the BRB-F:BFR-F binary combination resulted in dose-dependent improvement in AD-like skin lesions and reduced histopathological severity. The mixture suppressed Th2 cytokines (IL-4, IL-5, IL-13) in ear tissue and increased splenic Th1 cytokines (IL-2, IL-12, IFN-γ), accompanied by dose-dependent elevation of galectin-9, suggesting activation of Treg-associated pathways. IL-10 expression was also reduced in vivo. In vitro, BRB-F and BFR-F cooperatively inhibited IgE production by B cells, attenuated mast cell activation and TSLP release, and lowered keratinocyte secretion of TARC, MDC, and IL-6. Conclusions The combined oral administration of bioprocessed BRB-F and BFR-F exerts multi-targeted anti-atopic activity that includes modulation of Th1/Th2 immune balance, activation of Treg-associated signaling, and suppression of B-cell, mast cell, and keratinocyte responses. These findings, confirmed by histopathology of skin tissues before and after treatment, provide preclinical support for the development of BRB-F:BFR-F as a complementary functional material for managing immune dysregulation associated with AD, although validation in human patients will be required.