Background: The primary goal of the study was to create and statistically improve the proniosomal gel for increased transdermal administration utilizing 32 factorial designs to examine the influence of both non-ionic surfactant and phospolipon to maximize entrapment efficiency (EE) and cumulative release (CR). Methods: Formulation of resveratrol loaded pronisomal gel was done by coaservation phase separation method. Entrapment effectiveness and drug permeation were used as dependent factors, whereas the amount of surfactant and lipid were taken as independent variables. The components were examined at three different levels (1, 0, +1), each denoting a low, medium, and high level. Nine trial runs were examined and optimized for EE and CR based on the design. To further illustrate the effects of independent and dependent factors, contour and 3D charts were produced.Results: EE of resveratrol was found to be in the range of 79.57-94.51%. The Model F-value of 49.48 implies the model is significant. There is only a 0.02% chance that an F-value this large could occur due to noise.P-values less than 0.0500 indicate model terms are significant. CR of resveratrol loaded proniosome was found to be in the range of 58-82%. The Model F-value of 6.73 implies the model is significant. There is only a 2.93% chance that an F-value this large could occur due to noise. P-values less than 0.0500 indicate model terms are significant. Conclusion: According to the study, permeation flow depends simply on lipid concentration, but entrapment efficiency is dependent on both surfactant and lipid concentration. The results suggest that Resveratrol proniosomes can act as a promising carrier.