Commercially available p-aminobenzoic acid was used as a precursor for the synthesis of novel fused, non-fused, and spiro polyheterocyclic derivatives bearing indene, imidazole, pyrazole, and/or triazine nucleus via addition to simple and accessible reagents such as ninhydrin, o-phenylenediamine, and carbon disulfide. The experimental procedures were straightforward and simple, the products were isolated in 15–86% yields, and. their structure was confirmed by spectroscopic data. The synthesized compounds were evaluated for their antibacterial activity against some Gram-positive and Gram-negative bacteria.