Chlorpyrifos (CPF), an organophosphate insecticide has a wider application throughout the world to protect agricultural crops and vegetables from insects. Polyphenolic compounds are considered as beneficial against toxicities induced by organophosphates. The present study was conducted to understand the neuroprotective role of quercetin in chlorpyrifos‐induced apoptotic events in rats. Twenty‐four male Sprague Dawley rats weighing 170 to 200 g were divided into four groups viz: Control, chlorpyrifos treated (13.5 mg/kg body wt. alternate day), quercetin treated (50 mg/kg body wt. every day) and combined chlorpyrifos + quercetin treated. All the treatments were carried out for a total duration of 60 days. Protein carbonyl content and acetylcholinesterase activity were estimated in serum along with cerebrum and cerebellum to ascertain neurotoxicity. Further, for appraisal of neurodegeneration as a consequence of apoptosis, protein expressions of Bcl‐2, Bax, cytochrome c, caspase‐8, and caspase‐9 were assessed. The results showed that protein carbonyl contents were markedly increased in both serum and brain tissues (cerebrum and cerebellum) of chlorpyrifos‐treated rats when compared with control group and were appreciably improved upon simultaneous supplementation with quercetin. Further, chlorpyrifos treatment revealed a significant decrease in the enzyme activity of acetylcholinesterase in serum as well as in cerebrum and cerebellum, which however was increased upon concomitant treatment with quercetin. In chlorpyrifos‐treated animals, we have observed a significant decrease in the protein expression level of Bcl‐2, but a remarkable increase in the expression levels of Bax, cytochrome c, caspase‐8, and caspase‐9 in both cerebrum and cerebellum. Interestingly, when chlorpyrifos‐treated animals were supplemented with quercetin, a significant increase in the expression of Bcl‐2 and an appreciable decline in the expression levels of Bax, cytochrome c, caspase‐8, and caspase‐9 was observed. In conclusion, the present study advocates that quercetin may prove to be a useful candidate in containing the oxidative‐induced apoptotic events during chlorpyrifos exposure.