From essential to harmful, excess copper compromises aquatic vitality. Curcumin, a potent antioxidant bioactive, counteracts heavy metal toxicity. This study examines its role in modulating the NRF2-KEAP1 pathway to boost antioxidant defenses and mitigate apoptosis in kidneys of Channa punctatus exposed to environmentally relevant Copper concentrations (ERCC). 180 fully habituated fish were categorized into six groups: Group 1 served as control, Group 2 was treated with 3 mg/L Curcumin, Group 3 was exposed to ERCC (0.85 mg/L Copper), while Group 4, Group 5 and Group 6 received co-exposure to ERCC along with the escalating Curcumin concentrations of 1 mg/L, 2 mg/L, and 3 mg/L, respectively, over periods of 15, 30, 45, 60, and 75 days. Biochemical assays were conducted to evaluate oxidative stress markers (Reactive oxygen species, reduced glutathione, glutathione peroxidase, and lipid peroxidation), kidney damage indicators (creatinine), and genotoxicity (micronuclei). Additionally, transcriptional profiling assessed mRNA levels of apoptosis-related factors (p53, bax, apaf1, cas9, cas3 and bcl2), while histopathological examinations revealed changes in renal architecture. Molecular docking analysis confirmed Curcumin's strong binding affinity to KEAP1, providing insights into its role in activating the NRF2-KEAP1 pathway. The results indicated that Curcumin significantly (p < 0.05) reduced Copper-induced oxidative stress, improved antioxidant defenses, suppressed genotoxicity, modulated apoptosis, and maintained renal tissue integrity. These findings validate curcumin's potential in effectively combating copper toxicity in aquaculture, paving the way for enhanced fish health and improved food safety.