The functional components known as milk oligosaccharides are crucial in the milk of diverse animals. Increasing evidence of immunomodulatory effects of milk oligosaccharides suggests that they may have some therapeutic potential in allergy. Here, we assess the effect of 3′-sialyllactose (3′-SL) on symptomatology and immune responses in a β-lactoglobulin (β-Lg)-sensitized mouse model of food allergy. Furthermore, 3′-SL mixed with 2′-fucosyllactose (2′-FL) at weight ratios of 1:6 and 1 000:1 to explore whether they had a synergies effect on alleviate sensitization. The results showed that 3′-SL and the mixture of 3′-SL and 2′-FL can regulate immune response and intestinal homeostasis. The intervention of 3′-SL and its mixture with 2′-FL can alleviate the symptoms of dermatitis, significantly reduce the serum specific-immunoglobulin (Ig) E (s-IgE) and specific-IgG1 (s-IgG1) levels (P < 0.05), reduce the accumulation of mast cells in the jejunum and maintain the diversity of the intestinal flora. 3′-SL could alleviate sensitization in a dose-dependent manner, and 3′-SL and 2′-FL have a synergies effect in reducing allergy. This study presented here opens the possibility that 3′-SL and the mixture of 3′-SL and 2′-FL in the form of nutritional ingredients could be used as adjuncts to existing treatment approaches to relieve food allergy in infants.