Statement of the Problem: Phenytoin (PHT) has been known to promote wound healing in some medical conditions owing to its proliferative as well as anti-inflammatory effects. Yet, its application in oral lesions was less investigated.Purpose: The aim of this study was to evaluate changes in periodontal indices following the topical use of phenytoin in chronic periodontitis. Materials and Method: In this doubled-blind, randomized, split-mouth controlled clinical study, 20 patients with moderate to severe chronic periodontitis referred to Periodontology Department of Shahid Sadoughi Medical University of Yazd in 2014 were selected consecutively. After initial therapy (scaling and root planning and oral hygiene instructions), periodontal indices including bleeding on probing (BOP), periodontal pocket depth (PPD) and modified gingival index (MGI) were recorded. Gingival facial surface of two posterior sextants with at least two teeth with similar conditions, were selected randomly. Then one surface received PHT paste whereas the other side had placebo as control. Patients were received the mucoadhesive pastes under strict control by an examiner, twice a day for a week. Periodontal indices were measured 3 weeks after treatment. Data was analyzed with t-test and paired t-test by using SPSS 21 software.Results: It was observed that periodontal pocket depth was significantly more decreased in phenytoin side in comparison with placebo one (p< 0.05). In addition, inflammatory indices including bleeding on probing and modified gingival index declined more in the phenytoin group (p= 0.001 and p< 0.05 respectively).Conclusion: These encouraging results support the use of 1% phenytoin mucoadhesive paste as an adjunctive in periodontal treatment. Keywords ● Phenytoin ● Chronic periodontitis ● Mucoadhesive paste ● Wound healing