A series of new 2‐(2‐ethylpyridin‐4‐yl)‐4‐methyl‐N‐phenylthiazole‐5‐carboxamide derivatives (5a‐l) were synthesized and evaluated for their in vitro antimicrobial activities. Among the screened compounds, 5b, 5d, 5e, 5f, and 5j have shown promising antimicrobial activities against both bacterial and fungal pathogens. A molecular docking study was conducted to know the probable mode of action of synthesized derivatives for antimicrobial activity. The active compounds have shown excellent binding affinity toward DNA gyrase and lumazine synthase enzymes. The physicochemical properties of the synthesized thiazole‐carboxamide derivatives were calculated. It has displayed the potential to be a reasonable oral bioavailability drug as determined by Lipinski's rule.