The inclusion of tert-butyl alcohol (tBA) as a co-guest of clathrate hydrates in the presence of CH4, CO2, and N2 was investigated for its potential role in gas storage and CO2 sequestration. The 13C NMR, Raman spectroscopy, and powder X-ray diffraction revealed that the guest gas (CH4, CO2, and N2) + tBA + water systems form sII hydrates. The enclathration of tBA molecules in the sII large (51264) cages resulted in significant thermodynamic stabilization of the CH4 + tBA and N2 + tBA hydrates. However, the hydrate phase equilibrium curves of the CO2 + tBA hydrates were shifted to inhibited regions despite the participation of tBA molecules as a co-guest in the sII hydrate lattices. tBA was found to function as a thermodynamic promoter for both CH4 and N2 hydrates, whereas it functioned as a thermodynamic inhibitor for CO2 hydrate. The overall experimental results provide a better understanding of the thermodynamic behaviors, structural transitions, and guest distributions of the guest gas (CH4, CO2, and N2) + tBA hydrates for the potential use of tBA in gas storage and CO2 sequestration.