Nucleic acids are substantial macromolecules that regulate cellular activities at various stages of cell growth and regulation. These nucleic acids are categorized as DNA and RNA that show polymorphisms in structure such as duplexes, triplex, hairpin and G-quadruplexes. G-quadruplex structures are non-canonical structures formed by square planar arrangement of guanine bases, held together by Hoogsteen hydrogen bonds. Various regions in human genome contain G-rich sequences that have potential to form G-quadruplex structures, such as telomeric DNA, coding and non-coding region of various genes such as c9orf72, fmr1, c-Myc, c-Kit, Bcl-2, etc. Some of these regions are often required by cancer cells for their growth and proliferation. Due to their special structure, these G-quadruplexes provide well-defined binding sites for small molecules and have emerged as an interesting therapeutics in the field of oncology. Small molecules that can bind to G-quadruplex DNA and stabilize their structure could have potential to act as anti-cancer agents. With the aim to explore the potential of natural molecules as anti-cancer agents by stabilizing G-quadruplex structure, we studied the interaction of various flavonoids with human telomeric DNA (Tel-7) forming G-quadruplex structure. We have found that amongst all flavonoids used in this study, Quercetin binds with telomeric DNA (Tel7) with highest affinity. Solution structure of Quercetin – Tel7 complex reveals that it interacts and stabilizes Tel-7 structure through π-stacking at two sites: between T1pT2 and between G6pT7. Further, we have also derived the first solution structure for the complex formed between Quercetin and c-myc G-quadruplex DNA (Pu24T). This model revealed that Quercetin stacks at 5' and 3' G-tetrads of Pu24T and stabilizes it via π-π stacking and it also induces apoptosis-mediated cell death and down-regulates c-myc gene expression in HeLa cells. Apart from flavonoids, we have reported for the first time the interaction of an alkaloid, Piperine, with three DNA sequences of human forming G-quadruplex structures, viz. telomeric DNA, promoter regions of c-Myc and c-Kit. Piperine showed specificity for G-quadruplex DNA over duplex DNA with highest affinity for c-Myc DNA and it also causes apoptosis-mediated cell death that further emphasizes its potential as anti-cancer agent by targeting c-myc promoter region forming G-quadruplex structure.