In order to extend the scaffold of non-peptidic calpain inhibitor, we have designed and synthesized 14 chalcone derivatives categorized into two groups based on their structures. Compounds 7 ($IC_{50}=16.67{pm}0.42{mu}M$) and 8 ($IC_{50}=16.92{pm}0.14{mu}M$) in group A were most selective ${mu}$-calpain inhibitor over cathepsins B and L. On the other hand, compound 14 possessing furan ring exhibited inhibitory activities for ${mu}$-calpain ($IC_{50}=15.39{pm}1.34{mu}M$) as well as cathepsin B ($IC_{50}=20.59{pm}1.35{mu}M$). The results discovered implicated that chalcone analogues possessing proper size and functional groups can be a potential lead core for selective non-peptidic ${mu}$-calpain inhibitor. Furthermore, dual inhibitors for ${mu}$-calpain and cathepsin B can also be developed from chalcones by elaborate structure manipulation.