2-(Arylidene)-1-thia-4-azaspiro[4.5]decan-3-ones (3a-e, 4a-e) were synthesized from the 1-thia-4-azaspiro[4.5] decan-3-one through Knoevenagel reaction using the microwave method. In vitro, antibacterial and antitubercular screening of synthetic derivatives 3a-e and 4a-e revealed that compounds 3a and 4b are considerably potent as antibacterial agents against Escherichia coli with MIC = 50 μg/mL and MIC = 50 μg/mL, respectively. Compounds 3e and 4e possessed very good antitubercular activity with MIC = 0.47 μg/mL and MIC = 0.43 μg/mL. The results of molecular docking analysis supported the results of in vitro evaluation as against antibacterial protein compound 3a showed the lowest binding energy and against antitubercular protein, while 3e and 4e were highly attached?