The purpose of this study is to formulate hydrogels containing Acyclovir (ACV) that could be used in the local treatment of Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV) infections. Different mucoadhesive polymers were used as Carbopol 940, HPMC K15M and Pluronic F-127. The prepared hydrogels were evaluated for their in vitro drug release, rheological behavior, and mucoadhesive force. Increasing the concentration of each polymer increased the viscosity, mucoadhesion. The in-vitro drug release of mucoadhesive buccal hydrogels formulations were carried out for 6 hrs. Through the porcine cellulose membrane and release of optimized formulation was found to be about 98.7%. The best formulation F6 was selected because it produced the optimum mucoadhesive strength, mucoadhesive time, optimum viscosity, and no irritant. The mucoadhesive force of optimized formulation was found to be 1.0065 N and time 375 min with concentration 3% of HPMC.