This study aims to determine the interaction of PVA and HPMC on the mechanical properties of green betel leaf extract wound dressing, also determine the composition of PVA and HPMC on the optimum formula of wound dressing green betel leaf extract obtained by the D-Optimal Design method, and to determine the mechanical properties of the optimum formula obtained by the D-Optimal Design method. The type of this research is the research which includes the optimization of the formula to determine the optimal composition of the formula that produces the desired characteristics of the film preparation. Formula optimization is based on D-Optimal Design using the help of Design Expert DX 11 software. The optimization stages include preliminary experiments, formula design and response analysis, optimization, verification.