The study generally aimed to test the in-vitro antibacterial potential, hematological and histopathological responses of crude extracts of P. florida and V. volvacea in Nile tilapia against A. hydrophila. Compete Randomized Design was used in the study. Disc diffusion was used to test the antibacterial potential, Challenge test was conducted to measure the hematological responses of the mushroom extracts. And Descriptive method was used to identify the mycochemical properties and Rastopathological examination. One-way ANOVA was used to analyzed the antibacterial effect and hematological test, T-test was used to compare the means in pre and post-test challenge of differential WBC counts. Based on the results gathered, both mushroom species were detected with the presence of mycochemical properties sich as alkaloids, glycosides and tannins. Both mushroom sp are potential antibacterial agents against A. awvirophila. The effect of extracts in differential counts cf WBCs in Nile tilapia, there was a significant increase c€ lymphocytes and significant decrease of neutrophils and fomeocytes. Thus, both extracts might be ai potential -nunostimulant agents. Lastly, Histepathological examinations results from the liver and gills, scrphological findings were as follows; liver samples, Tl ssows swelling of hepatic cells and T2 shows normal hepatic ceils. Gill samples, both Tl and T2 shows inflammation and mecrosis. Keywords: Mycochemical Screening, Antibacterial, Hematological, Histopathological.