Fifteen seaweeds belong to 13 families and 6 orders of the rhodophyta were sampled for one year from April 2007 to March 2008 along the southwest coast of India (Indian Ocean). The species were examined forin vitro antimicrobial activity against six pathogenicVibrio strains isolated from moribund tiger shrimp (Penaeus monodon), six type cultures (Microbial Type Culture Collection, MTCC) of prominent shrimpVibrio pathogens, 10 multidrug resistant clinical pathogens, four species ofCandida obtained from pulmonary TB patients and four species of plant pathogenic fungi to evaluate their potency to be used as natural antibiotics in pharmaceutical and agriculture field. Bioactivity was analyzed from crude extract of fresh and dried samples prepared from different polar and nonpolar solvents. Of these, four species of red algae (Asparagopsis taxiformis, Laurencia ceylanica, Laurencia brandenii, Hypnea valentiae) were found to be highly active. Broadest and highest activity was observed in the crude extract ofA. Taxiformis. Among the pathogens tested, shrimp pathogenicVibrios were the most susceptible organisms while phytopathogens were found to be little resistant. In the present study, methanol was found to be the best solvent for extracting antimicrobial metabolites from dried samples rather than fresh. Seasonal variation in the antimicrobial activity was observed with higher level of activity recorded fromA. Taxiformis between December and January. The active principle ofA. Taxiformis was purified in column chromatography, TLC and reverse phase HPLC. The individual HPLC peaks were subsequently tested against a panel of pathogenic microorganisms and the active constituent was identified by GC-MS. The antimicrobial profile ofA. Taxiformis suggested that lipophilic compound which was primarily composed of pyrrole-2-carboxylic acid, pentadecanoic acid and octadecanoic acid might have functional role in the chemical defence against microbial invasion and these compounds could be utilized for the development of medically potential products.