The ancient literature of traditional Indian medicine indicate the potential medicinal values of Gmelina arborea as an important source of chemicals of enormous medicinal and pharmaceutical importance such as flavonoids, alkaloids, arboreol, isoarboreol, methyl arboreol, gummadiol, gmelanone, gmelinol, hexacosnol, n-octanol, β-sitosterol and luteolin. The present research has been undertaken with the aim to formulate and evaluate the herbal gel containing Gmelina arborea ethanolic leaf extract for antimicrobial properties. Phytochemical screening of Gmelina arborea reveals the presence of carbohydrates, alkaloids, saponins, tannins, anthraquinones and cardiac glycosides. The gel was prepared by using ethanolic leaf extract, Carbapol 934, methyl paraben, propyl paraben, propylene glycol, disodium EDTA, ethanol, triethanaloamine and distilled water. The physiochemical parameters of formulations such as pH, viscosity, spreadability and extrudability were determined. The results showed that the GF1 gel has better gel properties than other formulations. Determination of antimicrobial activity using the agar diffusion method showed that the crude extracts of the leaf and herbal gel of the plant inhibited the growth of recalcitrant pathogenic Staphylococcus aureus that frequently shows up in common skin infections. Neat ethanol extracts had the lowest minimum inhibitory concentration (MIC) of 0.01 μg each implying greatest activity against Staphylococcus aureus. Activity of the extracts was consistently less than the conventional antibiotic, tetracycline. Results provided the scientific basis for the folkloric application of G. arborea leaf extract for the possible control of skin infection associated with Staphylococcus aureus bacteria.