Plant flavonols are the best known class of naturally occurring organic molecules exhibiting ultrafast excited state intramolecular proton transfer (ESIPT) leading to 'two color' fluorescence emissions, which are exquisitely sensitive to the environment. On a different scenario, flavonols and related polyphenolic compounds of the flavonoid group, have attracted enormous attention as novel prophylactic and therapeutic drugs for free radical mediated and other human diseases. Their high potency and low cyto-toxicity make them viable alternatives to conventional therapeutics. In this context, identification of their physiological target molecules, mode of interactions with such targets, structure-affinity relationships and related aspects, have been key areas of investigations. This article presents perspectives, illustrating the potential usefulness of bioactive plant flavonols as their own fluorescence 'reporters' for exploring their interactions with duplex and quadruplex DNA molecules of potential interest as therapeutic targets. Representative and recent findings from our laboratory, and other relevant studies, exemplifying novel uses of flavonols as multiparametric fluorescence probes, are appropriately highlighted.