Ultrasound-assisted extract of Acalypha indica was used to prepare the green soap formulation. Previously, D-optimal mixture design was used to optimize the mixture of oil components including coconut oil (A, 34-56%), soybean oil (B, 19-31%), castor oil (C, 14-23%), sunflower oil (D, 4-6%), and olive oil (E, 5-9%). Linear regression models were proposed to predict the responses, i.e., hardness (Y-1), iodine (Y-2), and iodine number saponification (INS) (Y-3), and validated with a high degree of statistical accuracy (F-cal > F-tab; df = 4, p < 0.0001; R-2 > 0.9950). Optimization results revealed that the formulation containing 44.57% A, 23.62% B, 17.44% C, 5.37% D, and 9.0% E would yield 41 Y-1, 62 Y-2, and 159 Y-3. The chemical properties of the optimized soap formulation were quite comparable concerning the standard soap specifications (IS13498). Further, this formulation was supplemented with Acalypha indica extract to prepare the green soap, and its antifungal activity was determined using the agar dilution method.