Amyloid fibrils are deposited in various tissues in the body, and are linked to the putative causes of serious diseases such as amyloidosis. Although the conditions of the disease would be expected to improve if the fibril structure could be destroyed, the aggregated structure is stable under physiological conditions. Recently, we found that the amyloid fibrils of lysozyme could be refolded into their active form by using a mid-infrared free-electron laser (MIR-FEL) tuned to the amide I band (corresponding to the C=O stretch vibration), with the MIR-FEL having specific oscillation characteristics of a picosecond pulse structure, a tunable wavelength within mid-infrared frequencies, and high photon density. In the study, we tested the usability of the FEL for dissociation of aggregates of pathological amyloid fibrils by using a short peptide of human thyroid hormone. The fibrils (after being placed on a glass slide) were irradiated using the FEL tuned to the amide I band (1644 cm^?1), and those in situ were analyzed by Congo-Red assay, scanning-electron microscopy, and transmission-electron microscopy. All of the results obtained using these microscopic analyses indicated that the amyloid fibril formation was considerably decreased by FEL irradiation. Moreover, upon irradiation, a strong fibril peak at the amide I band in the infrared spectrum was transformed into a broad peak. These results imply that the β-sheet-rich structure of the amyloid fibrils changed into non-ordered or unspecified structures after the FEL irradiation. This FEL irradiation system, combined with various analytical methods, shows promise for the dissociation of amyloid aggregates.