<p>Alcohol consumption can affect the brain due to an elevation in oxidative stress and inflammation. Alcoholism influences the brain homeostasis and is often associated with cognitive, emotional and behavioral changes. Excessive alcohol intake can lead to poor sleep quality, and individuals with alcohol use disorder generally develop insomnia. Alcohol use affects the expression of clock genes, altering the physiological and immune function regulated by the biological clock, and hence elevating the production of reactive oxygen species. This study aimed to explore the alterations in neurobehavioral function associated with circadian disturbance and alcohol exposure, and to understand the potential therapeutic effect of methylsulfonylmethane on alcohol-administered and circadian-disrupted C57BL/6J mice. The sleep cycle of the mice was disturbed by 10&#xa0;h light/10&#xa0;h dark exposure, and 25% w/v alcohol was administered to the mice intragastrically. The concentration of trace elements in the mouse brain was measured using Inductively Coupled Mass Spectrometry (ICP-MS). An increase in anxiety-like behavior was observed in the mice exposed to alcohol and the circadian-disrupted groups. The administration of the drug significantly increased the expression of core clock genes in the alcohol and circadian-disrupted group. The levels of calcium and iron were increased in the MSM-administered mice, reversing the effects of circadian disruption and the alcohol-exposed group of mice. Our findings suggest that alcohol and circadian disturbance impact neurological function through alterations in immune homeostasis. MSM treatment can improve the expression of clock genes in alcohol and circadian-disrupted conditions, highlighting its neuroprotective potential by reducing inflammation.</p>