Aim: Aim of the present study was to evaluate the loading of clindamycin with injectable-guided tissue regeneration (GTR) will prevent the colonization of Porphyromonas gingivalis and to compare and assess the quantitative changes in P. gingivalis colony forming units (CFUs) by real-time polymerase chain reaction (PCR) analysis. Materials and methods: Thirty microbiological samples were pooled from the deepest periodontal pockets from the thirty sites from the two groups: group I—injectable GTR placed in the defect filled with demineralized freeze-dried bone allograft (DFDBA) and group II—clindamycin loaded injectable GTR placed in the defect filled with DFDBA. The total number of P. gingivalis CFUs was estimated using real-time PCR at baseline and 4 weeks after therapy. Results: A significant reduction in P. gingivalis CFUs at the end of 4 weeks was seen in both groups. Comparative evaluations between both groups at 4 weeks were with a mean of 4.44 ± 2.28 and 4.75 ± 3.32, respectively. Though there was a significant reduction in group II, the difference was statistically insignificant. Conclusion: The results suggest that clindamycin is beneficial in reducing microbial infection and can potentiate regeneration through host modulation. Clinical significance: Injectable GTR has the ability to mold according to the defect size and shape and eliminates the need to manipulate the membrane as required for the conventional membrane.