Supramolecular hydrogels made from guanine derivatives have attracted great interest for various applications. The gelation of guanine analogues usually involves the formation of guanine/K⁺ quartets. Functional cargoes such as fluorophores and drugs are usually decorated onto the guanine quartet gels via non-covalent π–π interactions or dynamic covalent linkages to render the gel with new functionalities. Here, a class of antiviral guanine quartet hydrogels have been developed via direct gelation of clinically available antiviral drugs such as entecavir, penciclovir, and ganciclovir in the presence of K⁺ ions. The prepared gels were stable at ambient temperature, non-toxic to normal cell lines, and maintained their inherent antiviral activities against hepatitis B virus and Herpes simplex virus, respectively. This study expands the function of guanine-based supramolecular gels and permits the development of a new class of antiviral gels.