Objective To study the anti-inflammatory effect of the co-cultured extracts of Lactobacillus salivarius and Yongchongcao [Cordyceps militaris (L.) Link] or Tiepishihu (Dendrobium officinale Kimura et Migo) on chronic skin eczema dermatitis. Methods L. salivarius was cultured in MRS medium with C. militaris or D. officinale. Then, the bacterial cells were fermented, crushed under high pressure, and centrifuged to prepare liquid medicine. Mice were randomly divided into control group, model group, positive drug group, co-cultured extract group of L. salivarius and C. militaris, and co-cultured extract group of L. salivarius and D. officinale. The eczema model of mice was established, and the degree of ear swelling, both ear quality difference and back skin thickness were measured. RAW264.7 cells and HaCaT cells were used as inflammatory cell models, and lipopolysaccharide (LPS) was used to induced the inflammatory responses. Effects of the co-cultured extracts of L. salivarius and C. militaris or D. officinale on the levels of interleukin-1β (IL-1β), nitric oxide (NO), interleukin-10 (IL-10) and skin inflammation biomarkersin in cells was evaluated. In addition, the phagocytic capacity of RAW264.7 cells treated with various extracts was determined. The MatTek human skin sensitivity test was selected to reveal the allergenic effect of the co-cultured extracts of L. salivarius and C. militaris or D. officinale. Results The difference in weight between left and right ears and dorsal skin thickness of mice in co-cultured extracts of L. salivarius and C. militaris or D. officinale were significantly lower than that in the model group (P < 0.01, 0.001). In parallel the production of inflammatory mediators (IL-1β and NO) and anti-inflammatory factor IL-10 were markedly regulated in cultured in RAW264.7 cells under the treatment of the co-cultured extracts of L. salivarius and C. militaris or D. officinale (P < 0.05, 0.01, 0.001). The rate of phagocytosis of LPS-induced RAW264.7 cells under the treatment was significantly reduced (P < 0.01, 0.001). HaCaT cells were treated with the co-cultured extracts of L. salivarius and C. militaris or D. officinale, the mRNA expression levels of the biomarkers of skin inflammation alpha-1 type I collagen (COL1A1), alpha-2 type I collagen (COL1A2), alpha-1 type III collagen (COL3A1) were significantly up-regulated (P < 0.05, 0.01). The co-cultured extracts of L. salivarius and C. militaris or D. officinale did not show allergy to human skin. Conclusion The co-cultured extracts of L. salivarius and C. militaris or D. officinale has anti-inflammatory and therapeutic effects on chronic skin eczema and dermatitis. They can be used as a raw material for anti-inflammatory and anti-allergic skin care products and has a strong application prospect.