As nonclassical nucleic acid structures, G-quadruplexes (G4s) not only play important roles in gene regulation and stability maintenance, but are also widely used in nanotechnology. Structural diversity is one of the main factors explaining the popularity of G4s, but a comprehensive and integrated study of different factors determining G4 structural versatility is currently lacking. Herein, starting from a common G4 sequence, (G 3 T) 3 G 3 , as the parent chain, and then taking advantage of G4 versatility, we present a variety of strategies to control G4 structure, based on the regulation of loop length and flanking sequences, cation (type and concentration), and molecular crowding. These strategies allow us to convert the G4 topology from parallel to hybrid, to antiparallel, and then back to parallel. Such structural diversity reveals the coding regulation ability of G4 structures, with potential applications in nanotechnology.