Periodontitis is an inflammatory disease of tooth-supporting tissues that is usually treated by mechanical removal of plaque and periodontopathic bacteria. Several studies have demonstrated that adjunctive therapy with locally delivered antimicrobials results in improved clinical outcomes. Our previous studies showed that Streblus asper leaf extract possessed an antimicrobial effect against periodontal pathogens. Objectives: the study assessed the in vitro release profile of gel containing Streblus asper, the antimicrobial effect against Actinobacillus actinomycetemcomitans and clinical safety. Methods: in this study, we developed a Streblus asper leaf extract gel (SA gel) and determined its antimicrobial effect in vitro. In addition, the most stable SA gel formula was selected for safety evaluation (phase I clinical trial study) in 30 volunteers. Results: our results showed that 24% SA gel (w/w) in hydroxyethylcellulose was the most stable formula with at least 6-month stability when stored at 4oC. Pharmacokinetic analysis demonstrated that the extract released from the gel approached to a zero order model. In addition, this SA gel formula possessed an effective bactericidal activity against the periodontal pathogen, A. actinomycetemcomitans, for at least 7 days. The results from the phase I clinical trial revealed that the SA gel formula offered ease of delivery to the periodontal pocket and that there were no significant local or systemic effects of the SA gel in the clinical application. Conclusions: within the limits of this study, it can be concluded that the SA gel possesses desirable antimicrobial property and safety, suggesting a potential use of this gel as an adjunctive periodontal therapy. Future clinical evaluations of this gel are warranted. This study was supported by grants from the Graduate School (Grant 4624102) and from Research Affairs, Khon Kaen University.