Periodontitis is a multifactorial infection associated with a variable bacterial pattern. The treatment focuses mainly on the reduction of the total bacterial count. Local delivery of antimicrobials has been investigated as an adjunct to conventional therapy. Tetracycline was proved to inhibit collagenases and was thus proposed to be useful in treating diseases. In recent years, silver nanoparticles have attracted considerable attention for medical applications due to their antibacterial activity. This study aims to evaluate the clinical and the microbiological findings following intrasulcular applications of tetracycline films and silver nanoparticles in periodontal pockets. A total of 48 periodontal pockets were studied. Group (A) received scaling and root planing with tetracycline film application, Group (B): scaling and root planing with silver nanoparticles application and Group (C): scaling and root planing only. The drugs were applied once weekly for three weeks. Clinical parameters were taken at baseline, after one and three months. Samples of gingival crevicular fluid were obtained at baseline and after one month for microbiological analysis. Groups A and B showed a significant decrease in probing depth and clinical attachment level as well as the reduction in the bacterial count compared to Group C. Thus, local application of tetracycline films and silver nanoparticles were effective in improving the clinical outcome and elimination of bacterial infection in periodontal pockets.