We describe here the in silico design, synthesis and biological evaluation of four novel effective 1-(3,6-dimethyl-4-phenyl-1H-indazol-5-yl)ethan-1-one derivatives synthesized from the treatment of hydrazine hydrates in MeOH/H+ with 1,1'-(3-hydroxy-4'-methoxy-5-methyl- [1,1'-biphenyl]-2,6-diyl) bis(ethan-1-one). The structures of all new compounds were confirmed by IR, ¹H NMR, ¹³C NMR, and mass spectral analysis. The synthesized compounds are screened for their antimicrobial, antioxidant activity, the compounds 1-(3,6-dimethyl-4-phenyl-1H-indazol-5-yl)ethan-1-one (5a), 1-(4-(3,4-dimethoxyphenyl)-3,6-dimethyl-1H-indazol-5-yl)ethan-1-one (5b), and 1-(3,6-dimethyl-4-(2,3,4-trimethoxyphenyl)-1H-indazol-5-yl)ethan-1-one 5d display prominent antimicrobial, antioxidant activity. Finally, a molecular docking analysis was performed to investigate the binding mode and interactions of the most active compounds to the active site of DNA gyrase enzyme 1KZN.