In this study, the inclusion of methane (CH4) gas in isoxazole (C3H3NO) clathrate hydrates was investigated through spectroscopic observations, such as powder X-ray diffraction (PXRD) and Raman spectroscopy. PXRD patterns of isoxazole clathrate hydrates having two different mole fractions of water were analyzed, and Raman spectroscopy was used to understand the CH4 inclusion behaviors in the hydrate cavities. Raman spectra indicated that CH4 can be captured in both small and large cavities of structure II hydrate in the C3H3NO with 34H(2)O system, while CH4 can be entrapped in only small cavities of structure II hydrate in the C3H3NO with 17H(2)O system. The PXRD result showed both clathrate hydrate samples exhibit the same cubic Fd3m structure II hydrate as expected. However, the structure II hydrate in the C3H3NO with 34H(2)O system includes a small amount of hexagonal ice and structure I CH4 hydrate. The phase equilibrium conditions of the binary (isoxazole + CH4) clathrate hydrate were also identified through high-pressure micro differential scanning calorimetry (MicroDSC), and the equilibrium temperatures of the binary (isoxazole + CH4) clathrate hydrate at given pressures are higher than those of the structure I CH4 hydrate.