Antimicrobials have many therapeutic, medicinal and industrial applications. However, restricted inhibitory spectrum of antimicrobials on distantly related species limits their wide applications. In the present study, authenticity of this contradiction had been investigated by evaluating amplitude of obstruction of indigenous antimicrobials of fish under different physical and cultural conditions against distantly related gram-negative pathogenic bacteria, Aeromonas hydrophila and Pseudomonas aeruginosa. Antimicrobials were examined for repression against pathogenic strains by agar well diffusion assay. Antimicrobials were more suppressive towards Aeromonas hydrophila than Pseudomonas aeruginosa. Antagonism by protein like thermolabile products was promising against Aeromonas. No inhibitions were outlined against gram-negative pathogens by protein like thermostable products. Native thermolabile proteinaceous antimicrobials of the present study are superior substitute for therapeutic applications over protective culture and antibiotics with least consequences on sensory, nutritional and microbial attributes of fish.