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The protein extract of Etroplus suratensis (E. suratensis) collected from Bavanisagar dam was found to be effective against all tested organisms with an inhibition zone ranging from 0.2 to 1.9 mm. When the result was compared with standard antibiotic Streptomycin, a moderate efficiency was observed. In vitro, an antibacterial assay was used to assess the efficacy of fish protein in inhibiting the growth of pathogenic microbes. The fish protein of E. suratensis collected from Bavanisagar had a broad spectrum of antibacterial potential. The minimal inhibitory concentrations of E. suratensis against pathogens are the highest in protein collected from Bavanisagar. In the fish protein collected from Bavanisagar, it has been shown that the minimum bactericidal concentration (MBC) value is higher in Bacillus subtilis (0.85/20 µg/ml) and the lowest in Micrococcus (0.1/100 µg/ml). The sub-lethal dose of fish protein was estimated at 1/10 of 96 h LD50 dose (30 µg/ml/Kg), the antibody response was significantly enhanced on day 14 and day 21 (p < 0.01). The highest IgG level was noticed on day 21, which decreased towards day 28. This result showed the antibody production with an increased IgG concentration. The above results demonstrate that fish protein extracts have great potential as immunostimulants against the microorganisms and they can be used in the treatment of infectious diseases caused by the microorganisms.