Polyampholyte (PA) hydrogels have attracted significant attention for their superior mechanical strength and toughness compared with other conventional hydrogels. In this study, we present a novel thermodynamic approach to understanding the mechano-chemo-electrotaxis coupling and interfacial dynamics in PA hydrogels. Flory-Huggins theory, carried out through an interfacial free-energy model, is the foundation for the quantitative study of the mechanically constitutive relationship of the PA gels. The proposed free-energy model is further extended to describe the mechano-chemo-electrotaxis switching and interfacial dynamics by co-relating the Williams-Landel-Ferry equation and scaling laws. It was concluded that the interfacial bonding strength is the key factor influencing the mechanical strength and reconstruction reversibility of the PA macromolecular gel system. The resulting analytical outcomes showed good agreement with the reported experimental data. We opine that the proposed model will guide the future application of PA hydrogels.