This work reports the synthesis, characterization of new (2E)-1-(biphenyl-4-yl)-3-aryl)-prop-2-en-1-one derivatives (C1-C10). The compounds exhibited moderate to good DPPH scavenging activity; amid those C5, C7 and C8 exhibited excellent scavenging activity. The chalcone derivatives were evaluated for their radioprotective activity in E.coli K12, in vitro. In C5 pretreated and irradiated E. coli K12 bacteria sample, the level of antioxidant enzymes SOD and CAT were restored to near basal level. It also showed significant demulating effect on the level of TBARS indicating good antioxidant activity. The chalcone derivatives were also evaluated for in vitro and in silico antibacterial and antifungal activities. All the compounds exhibited moderate to good antimicrobial activity at MIC 10-40 μg/mL. The compounds were docked at the active site of the antibacterial target methionyl-tRNA synthetase (metRS) (PDB ID: 1A8H) to predict their putative interactions. Among the tested compounds the compounds C3, C9 and C10 showed -4.7, -4.1 and -5.2 DG in Kcal/mol binding energies respectively.