Hydrogels are kinds of soft materials with 3D network structure, which play important roles in medical materials, such as contact lenses, surgical implants, wound dressings, artificial skin, drug release carriers, suture coatings, especially antibacterial materials that could solve problems of microbial infections. There are many studies on 18b-glycyrrhetinic acid (GA) derivatives hydrogel, but few on application in antibacterial materials. GA-O-20, one of GA derivatives, showed marvelous antibacterial property compared with its parent compound GA. Therefore, it was adopted as basic functional material to prepare supramolecular self-assembly hydrogels in the mixture solvent of water and ethanol. This hydrogel exhibits outstanding thermodynamic stability; the gel melting temperature (T gel ) is high to 96.6 ± 0.48 °C. Besides, it presented exceptional antibacterial that its minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) value are 6.25 and 12.5 lM, respectively, which was possibility caused by its sustained self-released property. This supramolecular self-assembly hydrogel may have enormous potentials in the application of antibacterial materials and drug delivery, which can be helpful to expand the application of GA derivatives.