The improper application of pesticides including fungicides generates serious biological risks that may compromise aquatic biota and inhibit sustainable aquaculture. Consequently, this pioneering attempt looked at the ability of the leaves of Malva parviflora (Egyptian mallow) powder (MPP) to counteract various toxicological consequences in Oreochromis niloticus (Nile tilapia) caused by metiram (MEM) exposure. The investigation encompassed neuro-ethology, stress biomarkers, gene expression associated with endoplasmic reticulum (ER) stress, and histopathology assays of gill and brain tissues. Accordingly, fish (32.80 ± 0.92 g body weight; n = 200) were haphazardly assigned into four groups in five replicates for nine weeks (control, MPP, MEM, and MPP + MEM). The nominal concentration of MEM was 0.377 mg/L (1/10 of 96 h-lethal concentration 50). Dietary MPP level was included at 15 g/kg diet concentration. The outcomes revealed lower fish survivability (68.00 %) and significant (P < 0.05) various behavioral changes (declining in foraging, swimming, aggressive and line crossing, and increasing in surfacing, resting, and abnormal movement) by chronic MEM exposure. The neurostress biomarkers were significantly (P < 0.001) altered by MEM exposure, where 8-hydroxy-2′-deoxyguanosine, glucose, and cortisol increased with no marked change in acetylcholine esterase activity. In addition, the MEM exposure induced a prolonged ER stress which was proven by significant (P < 0.001) up-regulation of Jun-Nterminal kinase, C/EBP homologous protein, and extracellular signal-regulated kinase-1 genes of gills and mechanistic target of rapamycin kinase, protein kinase RNA-like ER kinase, activating transcription factor 6, and binding immunoglobulin protein genes of brain. Histologically, it considerably generated a wide variety of changes in gills (detachment, inflammatory cell infiltration, and congestion) and brain (vacuolation, degeneration, and marked aggregation of glial cells). Interestingly, the dietary intervention of MPP significantly (P < 0.05) streamlined these variables by nearly renovating to control levels while preserving the histological integrity of the gills and brain tissues. The outputs of this perspective suggest the dietary intervention of MPP to safeguard against MEM toxicity in O. niloticus for sustaining aquaculture.