Microemulsions have been recognized as more effective compared to conventional topical treatments due to their transparent nature, stability, ease of preparation, and potential for large-scale production. These structured vehicles have the ability to solubilize drugs more effectively, enhance drug absorption into the skin, and improve drug delivery properties owing to their small droplet size and low interfacial tension. Enalapril is commonly administered orally as an antihypertensive medication; however, this study focused on formulating and characterizing microemulsions containing enalapril for transdermal application using non-ionic and nontoxic surfactants. A total of eight microemulsions were developed and evaluated for their rheological properties and droplet size. The permeation of enalapril through the skin was assessed using Franz diffusion cells, and an HPLC method was established to analyze the permeability. The efficacy of one of the microemulsions was tested on rat skin in comparison to oral administration. The findings revealed that the formulated microemulsions facilitated the permeation of enalapril through the skin, as demonstrated by the diffusion cells. The in vivo results highlighted the impact of absorbed enalapril through both transdermal and oral routes. The novel microemulsions display potential as carriers for facilitating the rapid and efficient administration of lower dosages during treatment.