Crystalline materials that are grown in gel media exhibit reinforced mechanical characteristics. Studies on the mechanical properties of protein crystals are limited in numbers because of the difficulty in growing high-quality large crystals. This study shows the demonstration of the unique macroscopic mechanical properties by compression tests of large protein crystals grown in both solution and agarose gel. Particularly, the gel-incorporating protein crystals exhibit larger elastic limits and a higher fracture stress compared with the native protein crystals without gel. Conversely, the change in the Young’s modulus corresponding to if the crystals incorporate the gel network is negligible. This suggests that gel networks affect only the fracture phenomenon. Thus, reinforced mechanical characteristics that cannot be obtained by the gel or the protein crystal alone can be developed. By combining the gel media and protein crystals, the gel-incorporating protein crystals show the potential to toughen without sacrificing other mechanical properties.