Food allergy (FA) has become a prominent problem in public health. 2'-Fucosyllactose (2'-FL) was reported to alleviate FA symptoms; however, the regulatory mechanism is still unclear. This study evaluated the 2'-FL antiallergic potential in an ovalbumin (OVA)-sensitized mouse model and explored the systemic effects of 2'-FL on gut microecology and the intestinal immune barrier. The results showed that 2'-FL alleviated allergy symptoms, decreased serum allergic indicator levels, enhanced the intestinal barrier, and attenuated low-grade inflammation. The up-regulation of G protein-coupled receptors (GPRs) was associated with higher levels of short-chain fatty acids (SCFAs) in 2'-FL intervention mice. 2'-FL also improved the intestinal microbiota diversity and increased the abundance of Akkermansia, Lachnospiraceae UCG-006, and Ruminococcaceae while suppressing Muribaculaceae, Desulfovibrionaceae, and Erysipelotrichaceae. Additionally, 2'-FL ameliorated the imbalance of Th2/Th1, mainly by decreasing Th2-type immune response and enhanced CD4 + Foxp3 + Treg immunoreaction. These results suggest that 2'-FL restores intestinal barrier defects, gut microbiota disorder, and immune impairment while alleviating ovalbumin-induced allergic symptoms in FA mice.