The aim of this study was to formulate and evaluate the novel amoxicillin trihydrate dental gel containing different hydrophilic polymers such as hydroxy propyl methyl cellulose (HPMC), methyl cellulose (MC), sodium carboxy methyl cellulose (Sod.CMC) and hydroxy propyl cellulose (HPC) in varied concentrations (5, 6, 6 and 9 %) for the treatment of periodontal diseases. Propylene glycol was used as a co-solvent in the concentration 15-25%. The formulated dental gels were found transparent, smooth and similar in color on physical observation. The pH of the dental gels was found to be in the range of 6.03 to 6.34. The spreadability of the gel was found to be in the range of 6.33 to 7.81 g-cm/sec. The viscosity values ranged from 4322.89 cps to 4665.78 cps. Drug content was found to be in the range of 95.93 to 99.31%. In-vitro drug release studies of formulations were carried out in the Kishery- Chein diffusion cell which exhibited an extended release of drug over a period of 7 hours. The pure drug and the best formulation were evaluated for antimicrobial studies by serial dilution method using nutrient broth medium. It was noticed that with increased drug concentration marked antimicrobial activity was achieved. Thus the present formulation of amoxicillin trihydrate dental gel could be suggested as a safe and beneficial dosage form for the treatment of periodontal infections.