The blocking ability of allergen-specific F(ab’)2 [sF(ab’)2] and Fab (sFab) fragment antibodies derived from allergen immunotherapy–induced specific immunoglobulin G (sIgG) has yet to be completely explored. In patients receiving subcutaneous immunotherapy (SCIT) for Dermatophagoides pteronyssinus (Der-p), the inhibitory activity of sIgG, F(ab’)2 [sF(ab’)2], and sFab antibodies was investigated. About 10 participants (ages 18 to 42) with house dust mite allergic rhinitis or asthma were given a 156-week course of Der-p SCIT in this study. Protein A affinity chromatography was used to purify total IgG levels from the subjects’ serum at weeks 0 and 156. At week 156, Der-p sIgG was isolated using affinity chromatography with Der-p as a ligand. Pepsin and papain were used to generate the SF(ab’)2 and sFab antibodies from Der-p sIgG, respectively. The inhibitory activity of Der-p sIgG, SF(ab’)2, and sFab antibodies was further assessed using an IgE-facilitated allergen binding assay, a basophil activation inhibition test, and a cytokine release inhibition assay. The Der-p sIgG, SF(ab’)2, and sFab antibodies significantly reduced the generation of interleukin (IL)-5, IL-13, IL-17, and tumor necrosis factor- by peripheral blood mononuclear cells, prevented basophil activation, and blocked Der-p–allergen sIgE complex binding to B cells. SCIT-induced Der-p sIgG, SF(ab’)2, and sFab antibodies might inhibit the formation of Der-p–sIgE complexes, making them viable allergen-targeted biologics candidates for allergic asthma treatment.