By using X‐ray crystallography, we show that the complexes Λ/Δ‐Ru(TAP)2(11‐CN‐dppz)2+ (TAP=1,4,5,8‐tetraazaphenanthrene, dppz=dipyridophenazine) bind DNA G‐quadruplex in an enantiospecific manner that parallels the specificity of these complexes with duplex DNA. The Λ complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn‐guanosine is adjacent to the complex at the 5′ end of the quadruplex core. SRCD measurements confirm that the same conformational switch occurs in solution. The Δ enantiomer, by contrast, is present in the structure but stacked at the ends of the assembly. In addition, we report the structure of Λ‐Ru(phen)2(11‐CN‐dppz)2+ bound to d(TCGGCGCCGA), a duplex‐forming sequence, and use both structural models to provide insight into the motif‐specific luminescence response of the isostructural phen analogue enantiomers. One Way or Another: Enantiospecificity was observed in the binding of the ruthenium polypyridyl complex Λ/Δ‐Ru(TAP)2(11‐CN‐dppz)2+ to the G‐quadruplex‐forming sequence d(TAGGGTTA). Crystallographic studies yielded the first crystal structure of a ruthenium‐bound G‐quadruplex and reveal that the quadruplex adopts an antiparallel topology in the presence of the Λ isomer, but retains its parallel conformation with the Δ isomer.