Siddha system is one of the traditional systems of India, contributing towards the health care of human society. In the present work one of the herbo mineral preparations Gandhaga Mezhugu, especially used in skin diseases is evaluated for its antimicrobial potential. Antimicrobial efficacy of gandhagam (Raw sulphur) as well as, purified gandhagam and gandhaga mezhugu were evaluated against six pathogens E. coli, P. vulgaris, K. pneumoniae, S. aureus, S. mutans, C. albicans which are associated with various disease conditions. The agar well diffusion was used to determine the sensitivity of the samples, whilst the micro-dilution method was used for the determination of the minimal inhibition concentration (MIC). Of the samples assayed, the samples of gandhaga mezhugu were observed to be the more effective against all the tested pathogens. The results provided evidence that the studied samples might be potential sources of new antimicrobial drug.