To unlock the potential of clathrates hydrate for versatile applications in energy and environmental application such as energy storage, gas separation, and novel functional materials, profound understanding of their hidden nature must be secured. In this study, we focused on the complex host-guest and heterogeneous guest-guest interactions occurring on the sH hydrates of 3,3-dimethyl-1-butanol with help gases of CH4 or CO2. The density functional theory calculations and spectroscopic experimental analyses showed that the dynamics of the large 3,3-dimethyl-1-butanol guest molecule as well as the host water frameworks of sH hydrate were significantly influenced by the type of gaseous co-guest molecules via complex host-guest and/or guest-guest interactions. The flexible hydrogen-bonded water framework underwent contraction or elongation in the O:H-O hydrogen and O-H polar-covalent bonds induced by distinct occupation patterns of the co-guest help gases, and it was observed that, depending on the type, the co-guest help gases triggered the transformation of torsional configuration of the hydrophobic moieties of the large 3,3-dimethyl-1-butanol guest molecule while the hydrophilic part was incorporated into the host water framework.