Solvent free mechanochemical approach is utilized to synthesise new cocrystals of chrysin using supramolecular chemistry based upon reliable synthons. Chrysin, a flavone nutraceutical with wide range of beneficial effects has critically low bioavailability on account of its poor aqueous solubility and consequently poor absorption from the gastrointestinal tract. The present study focuses on this critical aspect and has exploited non covalent interactions to prepare its cocrystals with cytosine and thiamine hydrochloride. Various techniques were used for characterization including Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR), Solid State NMR Spectroscopy (SSNMR) and Powder X-Ray Diffraction (PXRD). The molecules in the cocrystals crystallized in neutral forms and assembled in a molecular layer by means of hydrogen bonding which was confirmed by structural characterization. The cocrystals share a common supramolecular motif being the OH…Narom interaction, involving phenolic moiety of C7 functionality of the parent molecule. Approximately 3–4 fold increase in solubility and dissolution profile of cocrystals was observed which was further corroborated by improved in vitro and in vivo activities including antioxidant, antihaemolytic and anti-inflammatory thus, opening a new viable technique for the exploitation of useful phytonutrients.