Research of the gut microbiome and its role in disease has vastly increased in recent years. Despite residing in the gastrointestinal tract (GIT), the gut microbiome can induce systemic effects. The gut communicates with the brain via the bidirectional gut-brain axis, which has led to a linkage between the gut microbiome and various disorders, including the rare neurodevelopmental disorder, Rett syndrome (RTT). A variety of clinical presentations are seen in RTT, as are differing levels of severity. This variability has been linked to the presence of intestinal dysbiosis. An increased degree of dysbiosis has been seen to positively correlate with the severity of RTT. A proposed mechanism includes gut dysbiosis causing increased permeability of the GIT lining, allowing the entry of substances that invoke systemic inflammation, including neuroinflammation. Aside from neurodevelopmental symptoms in RTT, patients also have an array of GIT issues. A recent study observed that 80% of its RTT patients suffered from constipation, while 92% described general GIT issues. Specific to the gut, two separate studies of the microbiome in RTT patients found an abundance of Clostridium. Clostridium has also been found in abundance in autism spectrum disorder (ASD); like RTT, ASD patients commonly have GIT dysfunction. Additionally, patients with RTT often have gait difficulties, similar to Parkinson’s disease (PD). In a study of the gut microbiome in PD, an abundance of Enterobacteriaceae was observed. This abundance had a positive correlation with the severity of the gait impairment. This can be applied to RTT as patients from the aforementioned studies also had increases of Enterobacteriaceae. In short, other disorders can be used as a basis of comparison that will help elucidate the role of gut dysbiosis in RTT. First, the gut microbiome and RTT will be examined separately, allowing for a clear discussion into the mechanistic underpinnings of this potential relationship.