Objectives: While p-synephrine exhibits lipolytic activity, it also has a low oral bioavailability as well as hydrophilic characteristic, so it is difficult for it to penetrate the epidermis if it is made into transdermal preparation. The purpose of this research was to increase the penetration of p-synephrine by preparing it as transfersome gel. Materials and Methods: Three transfersome formulas were prepared—F1, F2, and F3—with the surfactants used at Tween 80, Span 80, and the combination of Tween 80 and Span 80 with a ratio of 1:1, respectively. Results: The results showed that F1 was the best formula, with the highest entrapment efficiency, of 64.058±0.754%, a particle size average of 103.3 nm, polydispersity index 0.269±0.05, and zeta potential of −36.2±0.64 mV, so this formula was employed for the gel formulation. Two gel formulas were then prepared, transfersome gel (GT) and non transfersome gel (GNT). Conclusions: The two gels were evaluated for their physical stability, and GT was found to be more stable than GNT. © 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd.