Shrimp aquaculture is the principal seafood product in international trade, and half of the total shrimp production was derived from aquaculture. Vibrio parahaemolyticus, is an opportunistic pathogen that causes symptomatic infections in shrimps as well in seafood. Phage has been proposed as bacterial pathogen controlling agents in a process called phage therapy. Phage particles are natural inhabitants of ecosystem so there is no harm or environmental hazards, while reintroduced into the same environment with enriched count. Based on our initial studies, three phages (VP1, VP7 and VP9) and pathogenic V. parahaemolyticus (BG 24) were taken. Two sets of experiments were conducted as phage (individual and cocktail) dispersed in water and mixed with fed diet to control V. parahaemolyticus infection in Penaeus monodon. According to phage treatment in water, 20% of shrimp mortality was observed. Other individual phage therapies VP1, VP7 and VP9 showed 30, 40 and 40% mortality respectively. During the phage fed diet experimental studies, shrimp immune parameters, gut phage count and bacterial count were monitored. Cocktail of phage fed shrimps produced a good haemocyte count and in control the cell count was drastically decreased. Similarly, total phenoloxidase and respiratory burst activity (superoxide anions) was observed high in cocktail phage treated shrimps. Lysozyme activity was gradually increased in all the phage treated group and significantly reduced in control. The cumulative survival rate stated that the cocktail phage fed shrimps survived 70% after 144 h and others 60–65%. Our results stated that phages also infect V. parahaemolyticus in the shrimp gut and its debris produce an immune response in shrimps, which can battle any infection non-specifically as immune stimulants. Application of phages as cocktile will improve the shrimp immune system and used as therapeutic and prophylactic measure for specific infection in shrimps.