A combinatorial synthesis of small libraries of a variety of amino chalcones has been carried out in solution phase under standard Claisen Schmidt conditions. The compounds were tested for their potential as antibacterial and cytotoxic agents as well as phosphatase inhibitors and the leads were identified in each bioassay. Chalcone 7 was found to have strongest potential as cytotoxic agent, while chalcone 11 be the most potent PGM inhibitory agent. Parallel synthesis of a 120 member chalcone library was carried out as mixture synthesis following the positional scanning protocol. The identification of lead in this library was carried out by deconvulution and chalcones 22 and 41 were found to be the most potential candidates to be developed as antibacterial agents. Following the same strategy of mixture synthesis, another 175 member chalcones library was synthesized and most potent anticancer chalcones 31, 61 and 78 were identified by deconvolution through position scanning protocol. Peptidyl α,β- unsaturated ketones were synthesized as novel bis- electrophiles susceptible for 3+2 and 3+4 annulations. As a result, peptidyl oxazoles, pyrazolines, pyrazoles, benzothiazepines and benzodiazepines were synthesized. Potent antidiabetic chalcones were docked into the PGM active site and a rationale was found for greater antidiabetic activity of chalcones over the other. Rational design and synthesis of some cytotoxic chalcones was based on 3DQSAR studies using CoMFA as a tool. 3DQSAR studies were also carried out on a library of 30 chalcones as potential antitumor agents.