The current study aims at examining the role of Mahua Oil (MO) as a permeation enhancing agents in gel formulation. Employing, erythromycin stearate, triethanolamine, ethanol, MO, DMSO, and water; two different gel formulations were fabricated. One formulation comprise of MO whereas the other contained DMSO as the permeation enhancer. Both the formulations were characterized in terms of viscosity, pH, extrudability, spreadability, skin irritability test, drug content, in vitro drug diffusion, and accelerated stability studies. The evaluation of formulation F2, which contain the MO, exhibited pH of 5.92, viscosity of 4090 cps, spreadability of 3.88 g.cm/sec, drug content of 98.11%, in vitro drug release of 95.64%, along with good extrudability. The accelerated stability study expressed no substantial alteration and skin irritation test showed no significant signs and symptoms. MO was relatively non-toxic, chemically inert, economic, widely availability, biodegradable, and demonstrate analogous attributes as compared to that of synthetic permeation enhancers. Therefore, a move towards utilizing excipients of natural origin represents a novel approach in formulating gel products in the future.