Erectile dysfunction (ED) is a prevalent condition influenced by vascular, psychological, and lifestyle factors. While PDE5 inhibitors remain a standard treatment, their systemic side effects necessitate alternative solutions. Reptile Gel, a topical formulation developed by West Bengal Chemical Industries Ltd., Kolkata, India (WBCIL), offers a fast-acting, non-invasive approach that enhances penile blood flow through an evaporative cooling and warming mechanism, stimulating nerve endings and promoting vasodilation. It is a non-drug topical application with no reported side effects and is approved as an over-the-counter (OTC) product by the USFDA. These unique selling propositions (USPs) make Reptile Gel a safe, convenient, and effective alternative to conventional ED treatments. The formulation, optimized with ethanol, propylene glycol, glycerin, and carbomer, ensures rapid absorption and a favorable safety profile. In this first clinical trial, we evaluated an advanced formulation of Reptile Gel developed by WBCIL, focusing on skin surface temperature dynamics as a marker of thermogenic activity. Temperature was measured at baseline and at 1, 10, and 15 minutes post-application, revealing a biphasic thermal response. These findings informed the design of a second ongoing trial, which will focus on Peak Systolic Velocity (PSV) assessment using Doppler ultrasound in a larger cohort to further investigate the gel’s vascular effects. As a CE-compliant medical device under the EU MDR framework, Reptile Gel presents a safe and effective alternative to conventional ED therapies, improving penile hemodynamics without systemic side effects. Reptile Gel effectively treats ED while boosting confidence, self-esteem, and relationships, offering a discreet, transformative solution for enhanced well-being.