Modified bases at designed positions of a G-quadruplex controlled the topology. Na+ stabilized an antiparallel G-quadruplex, whereas K+ destabilized this topology. The cosolute did not stabilized the antiparallel G-quadruplex with KCl. The cosolute did stabilize the G-quadruplexes with NaCl. How metal ions and cosolutes regulate G-quadruplex topologies was discussed.