An essential function of the gut-brain axis (GBA) is to control homeostasis and mental health. Operating through complex connections involving neurological, hormonal, and immunological pathways, the GBA is a key regulator of homeostasis and mental health. The interplay among oxidative stress, gut microbiota dysbiosis, and impaired barrier integrity suggests that disturbances in blood-brain barrier communication could significantly affect brain function in stressful circumstances. The impact of oxidative stress on the GBA is the main topic, along with its generation and the benefits of antioxidants. The causes of oxidative stress in the gut are examined, as well as how damaging it is to the integrity of the gut barrier, and furthermore, how this stress may result in the signals that cause the GBA to malfunction being transmitted. Numerous pathological conditions, including mental health issues like anxiety and depression, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s, have been linked to oxidative stress. The chapter emphasizes the inflammatory nature of modified GBA signaling, emphasizing how stress responses may compromise the integrity of the blood-brain and intestinal barriers. It also discusses the potential therapeutic benefits of dietary therapies, such as probiotic and antioxidant-rich diets, as well as lifestyle modifications and pharmaceutical approaches to support gut health.