A simple synthesis of novel 5-isatinylidenerhodanine-based furan derivatives via a multi-component reaction is described. The reactive 1:1 intermediate, produced by the reaction of tert-butyl isocyanide and dialkyl acetylenedicarboxylates, was trapped at reflux temperature by acidic derivatives of isatin and 5-isatinylidenerhodanine to yield isatin and 5-isatinylidenerhodanine-based poly functionalized furan rings in fairly good yields. The products were analyzed for antibacterial activity against Gram-positive and Gram-negative bacteria. The results indicate that the synthesized compounds are effective against bacterial growth retardation activity to some extent and their effectiveness is higher for Escherichia coli.