Particulate matter (PM2.5) is a risk factor for the deterioration of atopic dermatitis (AD) and certain constituents of PM2.5 can induce inflammation via oxidative stress. Natural functional foods, including antioxidative blueberry and black rice, can be the best alternative for the development of AD therapy. Thus, we investigated whether PM2.5 regulated the expression of proinflammatory cytokines involved in the progression of AD and further investigated the improvement effect of fermented blueberry and black rice extract (FBBBR) containing Lactobacillus plantarum MG4221 in vitro and in vivo. The FBBBR treatment significantly ameliorated skin inflammation compared with the control treatments via regulation of the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathways in PM2.5-treated HaCaT cells. In PM2.5/dinitrochlorobenzene (DNCB)-treated NC/Nga mice, the oral administration of FBBBR significantly decreased transepidermal water loss and erythema, the incidence of scratching behavior, and the production of serum immunoglobin E and T helper 2-associated cytokine and, similar to dexamethasone treatment, up-regulated the protein expression of filaggrin and involucrin in skin tissue. Syringic acid and kuromanin, standard compounds found in FBBBR, significantly decreased the interleukin (IL)-1β, IL-6 and IL-8 levels in PM2.5-treated HaCaT cells. Therefore, we can suggest that FBBBR may serve as an important functional food for AD.