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Background: Periodontitis causes the destruction of soft and hard tissues. Stem cells have immense potential in regenerative cellular therapy. This clinical trial aimed to evaluate clinically and radiographically the effectiveness of the local application of Edelweiss stem cells as a nonsurgical treatment for stage III periodontitis. Materials and Methods: The trial included 40 periodontal pockets in participants who have stage III periodontitis with probing pocket depth (PPD) ≥5 mm and clinical attachment loss (CAL) ≥5 mm. Pockets were randomly divided into two groups Group 1: was given oral hygiene instruction, scaling, root planing, and subgingival application of plant stem cells on gel foam carrier after that a periodontal dressing was applied. The procedures were repeated after 2 weeks. Group 2: was treated only by scaling and root planing. Gingival index, CAL, and PPD were measured at baseline and 3 months' posttherapy. The radiographical evaluation was done by digital long-cone parallel periapical radiographs at baseline and 6 months posttherapy. Results: Clinical parameters for both groups showed a statistically significant improvement. Regarding radiographic evaluation, there was a significant increase in bone density in favor of the study group. Conclusions: Locally applied Edelweiss stem cells can be considered a promising nonsurgical treatment modality for periodontal regeneration.