With the increasing development of plant–animal protein blended products, the nutritional complementarity of dual-protein systems has attracted widespread attention; however, their potential allergenicity still limits further application. To reduce the allergenicity of a soy–milk dual-protein mixture, an enzymatic modification strategy was applied using alkaline proteinase hydrolysis followed by cross-linking with transglutaminase (TG) or laccase (LAC). Single-factor experiments and response surface methodology were used to investigate the effects of enzyme-to-substrate ratio, temperature, reaction time, and pH of the two cross-linking enzymes after alkaline proteinase hydrolysis on the allergenicity of the mixed protein system (1:1, V/V). Changes in IgE-binding capacity and surface hydrophobicity of the mixed proteins were analyzed by indirect enzyme-linked immunosorbent assay (ELISA), immunoblotting, and 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence probe analysis. The results showed that under the optimal TG modification conditions of 49 °C, 2 h, an enzyme-to-substrate ratio of 5 U·g-1, and pH 7.5, the reduction rates of the two allergenic proteins were 71.36% and 87.03%, respectively. Under the optimal LAC modification conditions of 44.5 °C, 8 h, an enzyme-to-substrate ratio of 54 U·g-1, and pH 4.5, the corresponding reduction rates were 58.24% and 77.93%, respectively (P < 0.05). Both enzymatic treatments decreased the surface hydrophobicity, IgE-binding capacity, and molecular weight of the allergenic proteins in the mixed protein system, with TG showing a stronger effect than LAC. This study provides an experimental basis for process optimization and the development of hypoallergenic dual-protein products.