A natural flexible cyclic molecule, fangchinoline (FAN) from traditional Chinese medicine, was found with a good binding affinity and thermodynamic stabilization effect on a bcl2 G-quadruplex. Further studies showed that fangchinoline could induce the formation and the conformational conversion of G-quadruplexes from a mixed parallel/anti-parallel to a parallel stranded structure. Our study provided a novel G-quadruplex ligand facilitating the structural conversion of the G-quadruplex, which implied that this fangchinoline could be used to regulate biological activities of the G-quadruplex DNA.