Atopic dermatitis (AD) is a common inflammatory skin disorder for which few safe and effective systemic treatments are available. To test the clinical and immunomodulatory effects of a crude polysaccharide fraction isolated from Dendrobium huoshanensefor the treatment of AD, we conducted a pilot, uncontrolled case series study. Twenty-seven patients aged 4–18 years (mean±SD, 10.82±4.4) with AD that had not responded to topical therapy were treated with polysaccharide derived from D. huoshanensefor 4 weeks and followed-up for another 4 weeks. Progression of AD was determined with the Lund-Browder chart for children, the Investigator's Global Atopic Dermatitis Assessment (IGADA), and the Scoring Atopic Dermatitis (SCORAD) at weeks 0, 2, 4, and 8. Serum levels of cytokines were evaluated. Safety was determined with laboratory and clinical tests. The lesion area, IGADA score, total SCORAD result, and score for sleeplessness decreased significantly from weeks 0 to 4, but did not change significantly between weeks 4 and 8. The scores for subjective symptoms and pruritus decreased significantly from week 0 to week 4 and increased significantly from week 4 to week 8. Serum levels of IL-5, IL-13, IFN-γ, and TGF-β1 decreased significantly between weeks 0 and 4 and between weeks 0 and 8. No significant difference in the levels of IL-10 was found. The polysaccharide from D. huoshanensereduced the levels of some cytokines associated with AD and had beneficial effects on symptoms. No serious adverse effects occurred when it was administered orally for 4 weeks.