Inspired by nature, active materials are used to developed complex 3D configurations considering their specific characteristics. One of the shape-shifting methods in smart structures is utilizing programmable materials in self-folding structures. Hydrogels due to their biocompatibility, controllable functionalities, large reversible deformations, and their sensitivity to environmental stimuli are vital candidates to be used in self-folding structures. To avoid the mechanical weakness of conventional hydrogels, in this paper polyampholyte tough hydrogel is inspected considering a transient electro-chemo-mechanical constitutive model combining a visco-hyperelastic model with Nernst-Planck and Poisson’s equations. After calibrating the material parameters and verifying the accuracy of the model and its implementation, we present two approaches in order to generate self-folding hydrogel-based structures: polymer structure with bilayer hinges and trilayer structure composed of a hydrogel film sandwiched between two elastomer layers. Next, diverse factors are examined in the self-folding of smart structures which conforms with experimental test data, including hydrogel swelling, structure thickness and stiffness, bilayer configuration and composition, the width of the bilayer as well as opening width in trilayer and layers thickness. Finally, several transient self-folding of 2D flat patterns which turn into 3D complex configurations are scrutinized such as the closure of box, pyramids, and flower-shaper gripper.