Vibriosis is one of the most prevalent bacterial diseases leading to high mortality in cultured fish and shellfish. Recent reports reveal that secondary metabolites extracted from marine macro algae have defensive mechanism against infectious marine pathogens. This study exhibits the antibacterial and antioxidant efficacies of Portieria hornemannii extract using in vitro and in vivo assays. LD50 value of Oreochromis mossambicus (average body weight 10g) was found to be 9×10-5 cells/fish. The treatment was given by immersion of crude extract followed by experimental infection of Vibrio parahaemolyticus. The survival rate of the group treated with the P. hornemannii extract clearly demonstrated the therapeutic use in controlling Vibriosis. Histopathological analysis, clinical symptoms and antibacterial activity of P. hornemannii revealed the efficiency in controlling V. parahaemolyticus infection. The antimicrobial activity of the marine algae was analysed in order to appraise the productivity of methanol extract in discovering innovative bioactive compounds which can be passed down in aquaculture industry. Statement of relevance. Bioactive material extracted from the algae shows maximum antibacterial activity against V. parahaemolyticus in fish. The present study shows the preliminary results, in that compounds can work excellently in field levels, so that they can be incorporated along with feed for large scale application. © 2015 Elsevier B.V.