Background: The high density of farmed snakehead fish and the expansion of the farming area might cause a negative impact on water environment and an increased frequency of fish diseases. The use of plant-based extracts has been promised as an alternative method to antibiotic application in the controlling of fish diseases. This study was conducted to investigate the effect of Pleurotus ostreatus extract on survival, growth, immune responses and against Aeromonas hydrophila of snakehead fish (Channa striata). Methods: During 2021-11 to 2022-10, the P. ostreatus extract was prepared using hot water method and the fish fed diets supplemented the extract at 0.0 g kg-1, 1.5 g kg-1, 2.5 g kg-1, 3.5 g kg-1 and 4.5 g kg-1 was examined for survival rates, growth responses, white blood cell count, respiratory burst activity and mortality rates of fish in A. hydrophila infection. Result: The results indicated snakehead fish fed five different diets showed no significant differences in survival and growth performances. However, the innate immune parameters were likely increased in fish fed diets supplemented P. ostreatus extract and the diet supplemented extract at 4.5 g kg-1 could reduce the accumulate mortality of snakehead fish challenged with A. hydrophila. P. ostreatus extract could be a promising material for enhancing the innate immunity of snakehead fish and can protect fish from A. hydrophila infection.