Besides playing major role in cancer progression, nucleic acids are involved in various neuro-degenerative diseases caused by expansion of certain set of nucleotides. These expansions could be of trinucleotide repeats, tetranucleotide repeats, pentanucleotide repeats, hexa-nucleotide repeat and even dodecanucleotide repeats. These repeat expansion disorders share common pathogenic mechanisms: loss of function of the mutated gene, RNA toxic gain of function and protein toxic gain of function. Recently, a set of hexa-nucleotide repeat (GGGGCC)n in non-coding region of the c9orf72 gene was reported as the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The patients of ALS and FTD have common symptoms of cognitive impairments and subset of these diseases is characterized by formation of RNA-Protein foci. The pathogenic mechanism involves the formation of stable G-quadruplex or hairpin structure by expanded repeat transcripts (r (GGGGCC)n) of c9orf72 gene that provides a platform for binding of RNA Recognition Motif (RRM) containing proteins such as hnRNP A3, TDP-43, p62, SRSF1, etc. Sequestration of these proteins forms RNA foci in cells that lead to abortive transcripts formation and abnormal RNA processing that causes fatal disease condition. Thus, the rational discovery of bioactive small molecule that counterpoises these repeat transcript r(GGGGCC)n and prevents the formation of RNA foci would provide an effective therapeutics to cure ALS/FTD. We have found several small natural molecules with nano-molar binding constants for repeat containing target RNA by performing comprehensive biophysical studies such as steady state and time resolved fluorescence studies, CD and UV-melting experiments. Among all trinucleotide repeats expansion disorders, CAG causes the majority of disorders like Huntington's disease (HD) and spinocerebellar ataxia-3 (SCA3). We have reported the solution structure of RNA containing r(CAG) motif that reveals the dynamic behavior of non-canonical A-A pair. The structural information deduced by rMD studies has attracted the therapeutic approaches targeting these neurological disorders. We have screened several natural molecules targeting 5'CAG/3'GAC RNA motif to explore their specificity and affinity using various biophysical studies. Further, we have resolved the solution structure of RNA complexed with lead molecule that shows its specific binding for 1x1 AA nucleotide internal loops in 5'CAG/3'GAC RNA motif and could act potential therapeutic for targeting HD and SCAs.