Background: Catheter-associated urinary tract infections (CAUTI) constitute a significant portion of healthcare-associated infections. Using antiseptic for routine daily perineal care of patients with IUC may reduce CAUTIs. Aim: This study aimed to examine antimicrobial photodynamic inactivation (aPDI) against clinical isolates for use in the daily perineal care of patients with IUC. In addition, it was also aimed to compare the antimicrobial activities of aPDI and 0.1% chlorhexidine gluconate. Methods: In this in-vitro study, cationic porphyrin derivatives (CPDs) were used as photosensitizers in the experiments. CPDs, named PM, PE, PN, and PL were synthesized by the researchers. A diode laser device emitting light with a wavelength of 450 nm (blue light) was used as the light source. Methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Klebsiella pneumoniae with multidrug-resistant (MDR) properties and Candida albicans were used. Photosensitizer (PS), aPDI, light (L), and control (C) groups in aPDI experiments; control (C) and chlorhexidine gluconate 0.1% groups were used in the chlorhexidine gluconate experiments. Survival was calculated based on CFU/mL in the control group. Results: In experiments, combinations of 25 J/cm² with 6.25 and 3.125 µM PM, PE reduced E. coli, K. pneumoniae, MRSA, and C. albicans survival in the range of 8.70 to 11.53 log₁₀. In aPDI experiments performed with 6.25 and 3.125 µM PN and PL concentrations at the same energy density, reductions in the range of 4.41 to 0.17 log₁₀ were observed in all four clinical isolates. In experiments where 1.5625 µM concentration was used, survival decreased in the range of 8.29 to 10.87 log₁₀ in PM and PE, while antimicrobial activity was limited in PN and PL. In the 0.1% chlorhexidine gluconate experiments, the survival reduction in all four clinical isolates ranged from 8.87 to 10.24 log₁₀. Conclusion: For PM and PE, a very strong aPDI was obtained in C. albicans, E.coli, K. pneumoniae, and MRSA at low concentrations and energy density. The same antimicrobial activity was found in experiments using 0.1% chlorhexidine gluconate. In this context, we would like to inform you that aPDI to be performed with a combination of 25 J/cm² at 6.25 and 3.125 µM concentrations of PM and PE has the potential to be an antiseptic in the daily perineal care of patients with IUC.