Currently there are few amino acids hydrate based thermodynamic studies compared to kinetic studies, thus, the thermodynamic effect of four amino acids on methane hydrate formation are presented herein. The amino acids (valine, threonine, asparagine, and phenylalanine) were tested as gas hydrate inhibitors using the isochoric pressure search method in a high pressure stirring reactor. They were tested at 1 wt and 5 wt in the temperature and pressure ranges of 275.71�286.10 K and 3.52�10.25 MPa, respectively. All studied amino acids thermodynamically inhibited methane gas hydrate formation, with valine exhibiting the best inhibition impact with an average depression temperature of 0.529 K at 5 wt. Amino acids side chain properties were found to cause the variations in their inhibition impact. This study is useful to fully understand the thermodynamic inhibition effect of amino acids on gas hydrate formation. Inferring from the results in this study and literature, amino acids are thermodynamic gas hydrate inhibitors, while most of them are kinetic promoters. © 2018 Elsevier B.V.