Objective: To enhance the nutritional profile of Moringa oleifera leaves (MOLs), this study investigated the effects of MOLs fermented by Lactobacillus plantarum (MOLF) versus unfermented MOL powder (MOLP) on innate immunity and resistance to Aeromonas hydrophila challenge in Nile tilapia (Oreochromis niloticus). Methods: A 30-day feeding trial was conducted with 180 Nile tilapia fingerlings randomly assigned to five groups. The control group received a basal diet. Two groups received diets supplemented with low (50 g/kg) or high (100 g/kg) levels of MOLP, while the other two received similar levels of MOLF. Phenolic and flavonoid content was analyzed via HPLC. Results: Dietary supplementation with MOLF significantly (P<0.05) enhanced immune parameters compared to MOLP in a dose-dependent manner. MOLF increased serum nitric oxide and lysozyme levels, phagocytic activity, and hepatic antioxidant enzymes (SOD, GSH), while reducing malondialdehyde levels. Gene expression analysis showed significant downregulation of proinflammatory cytokines (IL1β, TNFα, IL-2) and upregulation of the anti-inflammatory cytokine IL-10 in immune organs post-challenge. MOLF-supplemented groups exhibited significantly higher survival rates and lower A. hydrophila bacterial loads. Conclusion: The findings suggest that Lactobacillus plantarum-fermented Moringa oleifera leaves (MOLF) are a promising dietary supplement for boosting immunity and disease resistance in Nile tilapia aquaculture