Sensing diffraction gratings of antigen-responsive hydrogel were developed for human immunoglobulin-G (H-IgG) detection. The IgG-sensing gratings were fabricated by soft lithographic duplication of photoinduced surface relief gratings on azo polymer films to the hydrogel surfaces. The quantitative detection of H-IgG was achieved by detecting modulation of the diffraction efficiency when the gratings were exposed to antigen solutions. The gratings showed high sensitivity and specificity for the H-IgG detection. The detection could be performed at a reasonably fast rate with good reusability. In the process, no fluorophore labeling or additional signal enhancement was required.