Background: The study of herbal medicine has grown tremendously in the last few decades. Because of its natural origin and minimal adverse effects. The polyherbal tablet formulation includes significant phytoconstituents like glycosides, alkaloids, Flavonoids, tannins, phenols, steroids, and terpenoids. These substances have a great chance of treating a wide range of diseases. Objectives: Development and Statistical Optimization of polyherbal tablets containing B. diffusa, E. prostrata, P. amarus, and S. nigrum hydroalcoholic entire plant extracts by applying 22 factorial design. Materials and methods: Selected entire plants were used for the preparation of hydroalcoholic extracts. The wet granulation techniques were used to prepare polyherbal tablets using HPMC, starch, and gelatin as a polymer. Results: Selected plant extracts were exposed to preliminary phytochemical investigation, which revealed the presence of steroids, alkaloids, glycosides, tannins, phenols, Flavonoids, and triterpenoids. The preformulation study's results on the granules' various parameters have been shown to be satisfactory. In order to optimize, 22 full factorial designs were used, with the amount of MCC (X2) and the amount of gelatin (X1) serving as the independent variables. The examination of hardness 6.125 kg/cm2 and friability 0.250% revealed that the F2 formulation was the most effective one. Conclusion: With an increase in MCC and gelatin content, the tablets' hardness significantly increased. The friability parameters are highly influenced by an ideal concentration of gelatin. When developing herbal tablets, a mixture of gelatin and MCC is the ideal combination of excipients. © 2024 Elsevier B.V., All rights reserved.