Staphylococcal enterotoxins (SEs) are kinds of bacterial exotoxins with vomiting activity secreted by S. aureus, which can cause diseases such as inflammation and food poisoning. SEs possess superantigen activity and can form ternary complexes with the variable region of T-cell receptor (TCR) and MHC class II molecule, i.e., TCR-SEs-MHC class II molecule, which could directly stimulate up to 30% of T lymphocytes to produce a large numbers of cytokines such as tumor necrosis factor-α (TNF-α), interleukin 2 (IL-2), IL-6, and interferon γ (IFN-γ), resulting in toxic shock syndrome (TSS). Among the common SEs, staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) are the most studied due to higher toxicity and frequency in reported incidents. Specially, about 70% of S. aureus food poisoning are caused by SEA, while, SEB was listed as an offensive biological warfare agent in 1960s. At present, there are few comprehensive review paper on treatment strategies for SEs poisoning. Hence, the review firstly introduces the classification, structure, and toxic effects of SEs, and then the ternary complexes of TCR-SEs-MHC class II molecular interaction sites are analyzed focusing on SEA and SEB. Furthermore, we summarize the recent advance in the filed of active and passive immunotherapy for SEs poisoning around SEA and SEB. We highlight the state of art and new developments on active immunotherapy mainly includes attenuated vaccine, subunit vaccine and other vaccines and passive immunotherapy that is mainly based on monoclonal antibody and genetic engineering antibody. Finally, we discuss and prospect the current limitations and future development of immunotherapy for SEs including synthetic peptide vaccine, single cell technology and nanobody isolation.