A new series of 2-[(substituted benzylidene)imino]-3-(N-methylcarboxamido)-4,5-trimethylene thiophenes were synthesized by the reaction of aliphatic ketone with cyanoacetamide in strong basic medium followed by Schiff base formation. Then newly synthesized compounds were characterized by IR spectroscopy, 1H NMR and mass spectral data. The newly synthesized compounds were screened for antifungal and antibacterial and anti- inflammatory activities. Among them ss6a, ss6f, ss6k and ss6l exhibited good antifungal and antibacterial activities and ss6d & ss6i showed promising anti-inflammatory activity.