Background Candida albicans infection induces economic losses in aquaculture practices. Currently, the success of the nanotechnology field has gained more consideration in the aquaculture sector as it bestows favorable impacts in remedies in comparison to traditional practices. Objective The present study was conducted to assess the role of nano chitosan gel (NCG) exposure via water in managing the deteriorating impacts triggered by C. albicans in Nile tilapia, Oreochromis niloticus. Hepato renal function, behavioral and stress response, neurological function, hepatic antioxidant/oxidant status, and histopathological architectures were investigated. Methods A total of 160 fish (average weight: 50.00 ± 6.30 g) were randomly assigned to four groups, each with four replicates: control, NCG, C. albicans, and NCG + C. albicans. The NCG was applied as bath treatment at a concentration of 75 µg/L for ten days. Results The outcomes demonstrated that the C. albicans challenged fish exhibited obvious behavioral alterations including loss of equilibrium, surfacing, abnormal swimming and movement, and aggression. Infection with C. albicans caused an elevation in hepato-renal biomarkers (alanine and aspartate aminotransferases, alkaline phosphatase, urea, and creatinine), stress-related indices (glucose, cortisol, nor-epinephrine, and 8-hydroxy-2