Tropomyosin (TM) is the most important allergen in shrimps that could cause food allergy. Glycation is reported to be effective in reducing TM allergenicity and produce hypoallergen; however, up to now, there are very few reports on the potential of hypoallergenic glycated TM (GTM) as allergen immunotherapy for shrimp TM-induced food allergy. This study investigated the glycation of TM-produced hypoallergen and the immunotherapeutic efficacy of GTM + Al(OH)3 as potential allergen immunotherapy. Compared to TM, the TM glycated by glucose (TM-G), maltotriose (TM-MTS), maltopentaose (TM-MPS) and maltoheptaose (TM-MHS) had weaker allergy activation on mast cells and mouse model as a hypoallergen. However, the TM glycated by maltose (TM-M) insignificantly affected the allergenicity. In addition, the GTM absorbed into Al(OH)3 could be efficacious as potential allergen immunotherapy, particularly for the TM glycated by the saccharides having larger molecular size (e.g., TM-MHS), which could provide preclinical data to develop GTM + Al(OH)3 as a candidate immunotherapy for shrimp allergic patients.