Piper betle L. is a perennial, dioecious and tropical shade loving creeper, belonging to the Piperaceae family. Piper betle is cultivated extensively in India and China due to its well-established roles in timeworn practices along with the plant__ampersandsignrsquo;s immense medicinal properties, establishing it as economically important. The antimicrobial role of Piper betle extract in topical formulation was not reported in any standard databases such as Google Scholar, PubMed, Science Direct, etc. The Piper betle-incorporated ointment formulations (B1-B5) containing various bases (hydrophilic ointment base, blend ointment base, macrogol cream base, simple ointment base, and white petrolatum base) were developed. The formulation showed desired physical appearance, spreadability, pH, extrudability, viscosity, and washability. The products were found to be non-irritant on human skin. The optimized formulation (B3) demonstrated no substantial disparity in the pH, viscosity, spreadability, swelling index, extrudability, and physical appearance which indicated desirable stability for the duration of 90 days under conditions of 40__ampersandsigndeg;C__ampersandsignplusmn;2__ampersandsigndeg;C, 75%__ampersandsignplusmn;5% RH. P. betle extract showed moderate anti-microbial activity against E. coli, B. subtilis, K. pneumonia, C. albicans, and A. niger. In the case of evaluation of anti-fungal potentials, significant growth inhibition was presented by the P. betle extract against C. albicans and A. niger.