Introduction: Oxidative stress plays a vital role in the development of neurodegenerative disorders, including demyelination. Quercetin, a natural flavonoid with antioxidant properties, has shown promise in mitigating oxidative stress. Additionally, the inhibition of inflammasome 3 (MCC950), a key component of the inflammatory response, has emerged as a potential therapeutic target. This study aimed to investigate the effect of quercetin and MCC950 on oxidative stress in a cuprizone model. Methods and Materials: Thirty C57 mice were divided into five groups: a healthy control group and four cuprizone-treated groups. Cuprizone was orally administered at a rate of 0.2% (w/w) for six weeks. Subsequently, the groups were treated as follows: Group 2 received saline, Group 3 received quercetin, Group 4 received the MCC-950, and Group 5 received a combination of quercetin and MCC-950. Oxidative stress parameters were assessed through biochemical tests including total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activity performed on brain tissue samples. Data analysis was conducted using GraphPad Prism 6.1. One-way ANOVA analysis followed by the Tukey post hoc test was applied to analyze the data. Results: Cuprizone administration induced a significant increase in oxidative stress markers compared to the control group (p < 0.05). Quercetin, MCC-950, or their combination showed promising trends in reducing oxidative stress levels. These interventions increased TAC, decreased MDA, enhanced SOD activity, and CAT activity (p < 0.05). Conclusion: Our findings suggest that quercetin and MCC950 may have potential in attenuating oxidative stress in the cuprizone-induced demyelination model. Further studies are needed to validate these results and explore the underlying mechanisms. The use of the inflammasome 3 inhibitor (MCC-950) also showed potential in reducing oxidative stress. These preclinical findings provide insights into potential therapeutic strategies for neurodegenerative diseases associated with oxidative stress, although further research is necessary to ascertain their clinical applicability.