Modern medicine is exploring new approaches to combat bacterial infections associated with antibiotic-resistant bacteria and biofilms. Among these, antimicrobial photodynamic therapy (aPDT) stands out for its ability to target pathogenic microbes effectively. In this study, we investigated the antimicrobial potential of the newly synthesized indium metalated pyridinyl-based trans-A2B2 porphyrin complexes, 1a,b and 2a,b. The dicationic porphyrins, 1b and 2b, exhibited remarkable aPDT efficacy against both S. aureus and E. coli planktonic forms. Further investigation into the antimicrobial effects of the cationic porphyrins against E. coli and S. aureus biofilms revealed that both complexes (1b and 2b) exhibited high efficacy in aPDT attributed to tert-butyl and thiophene groups that enhance photo-physicochemical properties and bacterial membrane accumulation. Scanning electron microscopy (SEM) showed disruption of cell membranes following light exposure. Our work highlights the potential of aPDT as an effective strategy for managing biofilms. By harnessing the power of these innovative compounds, we contribute to the ongoing battle against microbial threats.