Introduction: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by social interaction challenges, communication difficulties, and repetitive behaviors. While ASD lacks a cure, there is a growing interest in supplements, notably probiotics, for potential benefits. Probiotics are live microorganisms with health potential due to their role in the gut microbiome. Gut-brain axis is a bi-directional communication system that connects the gastrointestinal (GI) tract and the brain. Objective: This comprehensive review systematically searched scientific databases up to September 2023 to examine the use of supplements, particularly probiotics, in individuals with ASD. The review focused on addressing gut-related issues and improving behavior, speech, and overall well-being. Methods: A systematic search across databases such as PubMed, PsycINFO, and Cochrane library was conducted using keywords like "probiotics," "supplements," "ASD," "gut dysbiosis," and "therapeutic interventions." Studies meeting inclusion criteria, including clinical trials, observational studies, and case reports, were considered. Results: Several studies suggest that probiotics may improve behavior, brain activity, and eye contact in individuals with ASD by addressing gut dysbiosis. Lactobacillus reuteri and specific Bifidobacterium strains are recommended probiotics, but more research is needed to confirm their efficacy. This review also explores supplements like Vitamin B6, magnesium, Vitamin B12, Vitamin C, and Omega-3 fatty acids, which show potential in supporting speech and overall well-being in individuals with ASD. However, they are not a cure and should be used under professional guidance. The article also discusses supplements for adults with ASD, underlining the importance of consulting healthcare professionals before use and the necessity for further research to determine effectiveness and optimal dosages. Conclusion: Probiotics and supplements offer potential benefits for individuals with ASD, but they should be seen as complementary therapies rather than cures. A holistic approach, including medical supervision, therapy, and dietary considerations, is crucial for addressing the complex needs of individuals with ASD. Further research is necessary to uncover the precise mechanisms and therapeutic potential of these supplements in enhancing the lives of those with ASD. Categories: Neurology, Gastroenterology, Nutrition