Guest-induced structural transformation in amine semiclathrate hydrates is a unique pattern caused by modifying the hydrophobic-hydrophilic balance, and thus, it can be applied to potential gas storage and transportation areas. The experimental results of the structural transformation of isopropylamine (IPA) semiclathrate hydrates in the presence of methane (CH(4)) as a coguest are presented with a focus on the macroscopic phase behavior and microscopic analytical methods such as powder X-ray diffraction (PXRD) and NMR spectroscopy. The introduction of CH(4) molecules as coguests changed the structure of the IPA·8.0H(2)O semiclathrate hydrates (hexagonal, P6(3)/mmc) to sII gas hydrates (cubic, Fd3m). The microscopic analysis results indicate that the guest gas distribution and the clathrate hydrate composition can be altered with adjustment of the IPA concentration. The overall experimental results are valuable for increased understanding of the stability conditions, structural details, and guest-host interactions in hydrophobic guest gas + IPA clathrate hydrates.