Abstract: Background and Objective: The side effects of antibiotics on fish and the consequences on the environment can be mitigated using plant extracts. This study was conducted to evaluate the efficacies of mango leaf extracts on pathogens isolated from African mud catfish Clarias gariepinus. Materials and Methods: Sub adult catfish collected from private fish farms in Odogbolu, Ogun state, were used for microbiological examination, biochemical tests, DNA extraction and molecular characterization of bacteria. The fish were infected with Pseudomonas aeruginosa with visible lesions on flesh and subsequent treatment with Mangifera indica leaf extracts. Qualitative and quantitative phytochemicals were later determined. Haematology and histological studies carried out and Complete Randomized Design experiment was used for the study. Dissolved oxygen, pH and temperature were monitored weekly on the experimental farm. Data were analyzed using Analysis of Variance. Results: Haematological profile of WBC (White Blood Cells), HGB (Haemoglobin), RBC (Red Blood Cells) and HCT (Haematocrit) after treatment with extracts improved significantly after post infection at 10 mg mL–1 with liver normalizes after 7 days of treatment with mango leaf extracts at 10.0 mg mL–1 concentration. There was also, atrophy or proliferation of the epithelial cells of secondary lamellae with fusion 7 days after treatment at 10 mg mL–1. Phytochemicals present were alkaloids, flavonoids, saponin, tannin, cardiac glycoside, phenol, anthraquinone, terpenoid, phylobatanin and steroid. Quantitatively alkaloids were 10.49±1.00a, flavonoids 2.93±1.00ab, saponin 3.52±1.00ab, tannin 3.52±1.00bcd and phenol 4.10±1.00abc. Conclusion: This study revealed that mango leaves extracts at 10 mg mL–1 contained sufficient phytochemicals that exerted antibacterial properties on the identified fish pathogens and reduce reliance on synthetic antibiotics. It is therefore suffice to say that plant extracts are a good source of novel products and can serve as alternative to antibiotics.