Background: Pizza, an Italian culinary delight, is relished by diverse groups of individuals. In this study, pizza base was innovatively crafted by substituting refined wheat flour (RWF) by combining with little millet flour (LMF) and proso millet flour (PMF) along with Bacopa monneri. Methods: A meticulous investigation was conducted to assess the impact of different quantities of RWF (20-40 g), LMF (20-40 g) and PMF (20-40 g) on the quality attributes of the pizza base, using a D-optimal design for optimization. Result: The findings revealed that an increased proportion of refined wheat flour (RWF) enhanced the overall acceptability of the pizzabase. Further more, the hardness of the pizzabase was influenced by higher RWF quantities and reduced levels of proso millet flour (PMF) and little millet flour (LMF). Similarly, an increase in the amount of PMF led to a significant increase in both protein and antioxidant content. The optimized proportions for RWF, LMF and PMF were determined to be 40 g, 33.3334 g and 26.6666 g, respectively. This optimization yielded the following outcomes: an overall acceptability score of 8.33, an antioxidant content of 92.2727%, a pizza base texture (hardness) of 2388.88 g and a protein content of 10.3131%. These results are in concurrence with the predictions made by the significantly (p less than 0.05) fitted quadratic models.