Purpose <p>A clinical trial was conducted to explore the clinical and microbiological efficiencies of indocyanine green mediated photodynamic therapy (IG-PDT) and Laser curettage of soft tissue lining of periodontal pockets as adjunct to root surface debridement (RSD) for treating moderate-deep periodontal pockets.</p> Methods <p>This randomized, double-blind trial followed split-mouth design in which periodontal pockets (4–6&#xa0;mm) in three different sextants received either RSD only or with adjunctive IG-PDT or Laser curettage. Clinical parameters were recorded at baseline and after 3 months While collecting subgingival plaque samples were additionally performed after 1 month. Bacterial load of <i>Fusobacterium nucleatum</i> and <i>Fretibacterium fastidiosum</i> were assayed using PCR technique.</p> Results <p>The 17 stage 3 periodontitis patients exhibited significant improvements in clinical and microbiological parameters 3 months after treatment in all groups. The mean changes of PPD and CAL for RSD-treated teeth were 1.44 ± 1.11 and 0.52 ± 1.26, For IG-PDT 1.43 ± 1.19 and 0.65 ± 1.16, and for Laser curettage 1.38 ± 1.16 and 0.35 ± 1.32. No significant differences in microbiological outcomes between all groups except for significant reduction of <i>F. nucleatum</i> (1.5-2-fold) in sites treated with IG-PDT as compared to other groups (<i>p</i> &lt; 0.05). Regression analysis indicated that successful pocket closure is associated with the initial pocket depth and level of <i>F. nucleatum</i> at baseline regardless of treatment applied.</p> Conclusion <p>Combining IG-PDT with RSD had a profound effect in reducing bacterial load of <i>F. nucleatum</i> in moderate-deep pockets which could positively improve clinical outcomes on a longer term. Additionally, pocket closure was relatively enhanced in sites treated with IG-PDT.</p> Trial registration number <p>Clinicaltrials.gov (ID: NCT06305533) in 8/03/2024.</p>