The main aim in periodontitis treatment is to remove supragingival and subgingival biofilm. Mechanical treatment to eliminate pathogenic bacteria is limited by morphological conditions on the root surface. This study assessed the antibacterial effectiveness of different laser-based photochemical systems, particularly a novel curcumin-based option.Ninety-one titanium bars were inoculated with an artificial biofilm of common pathogenic periodontal bacteria and inserted into an artificial periodontal pocket model. The following groups (n = 13) were tested: 1, curcumin solution plus SLB laser irradiation (C + L; 445 nm, 0.6 W, 25% duty cycle, 100 Hz, 10 s); 2, curcumin solution (Cur); 3, dimethyl sulfoxide solution (DMSO); 4, SiroLaser Blue (SLB) - laser irradiation (445 nm, 0.6 W, 25% duty cycle, 100 Hz, 10 s); 5, antimicrobial photodynamic therapy (aPDT); 6, antimicrobial photothermal therapy (aPTT); 7, control. The samples were stored in Eppendorf tubes and analyzed microbiologically using quantitative real-time polymerase chain reaction (PCR). The main parameter for analyzing group differences was the total bacterial load. Statistical analysis was performed with nonparametric methods.Statistically significant reductions in bacterial count were observed in all experimental groups (p < 0.05). The mean percentage reductions were as follows: SLB, 95.03%; aPDT, 83.91%; DMSO, 95.69%; C + L, 97.15%. No statistically significant differences in bacteria reduction were observed for laser alone (SLB), DMSO, or curcumin with or without additional laser irradiation.The greatest antibacterial efficacy was observed in samples treated with aPTT. Using curcumin as a photosensitizing agent for 445 nm laser irradiation did not result in improved antibacterial effectiveness in comparison with laser alone.