While the neuromodulatory efficacy of n-3 polyunsaturated fatty acids present in fish and fish oil (FO) are well known, some evidence in animal models suggests that chronic consumption of FO supplements may predispose the brain to lipid peroxidation. In view of this, recent approaches envisage the use of dietary antioxidants as adjuncts with FO to obtain a better clinical outcome in neurological disorders. In furtherance of our previous work, in the present study, we examined whether enrichment of FO with quercetin (Q) would enhance the neuroprotective outcome employing a chronic rotenone (ROT) model of neurotoxicity in rats. Growing male rats supplemented either with FO (2 mL/kg bw) or Q (25 mg/kg bw) or FO + Q for 28 days were administered with ROT (0.5 mg/kg bw, 21 days). Monitoring the behavioral phenotype by a battery of tests, terminally, oxidative response in brain regions, mitochondrial dysfunctions and striatal dopamine levels were determined. While both FO and Q offered varying degree of protection, the FO + Q combination offered a higher degree of protection. FO + Q combination significantly attenuated behavioral impairments, restored the ROT-induced oxidative markers, depleted dopamine levels in striatum and reduced mitochondrial dysfunction. These salient findings besides corroborating with our previous data suggest that enrichment of FO with Q indeed offers a higher degree of neuroprotection under chronic exposure to a model neurotoxin such as ROT. Hence, we propose that a combination of FO with known antioxidants such as quercetin is more likely to provide a superior therapeutic advantage in the prevention/treatment of oxidative stress-mediated neurodegenerative conditions such as Parkinson’s disease.