<p>Various physiological and pathophysiological conditions, including metabolism, immunological tolerance, behavior, and cardiovascular disease, can be studied and manipulated by the complex human microbiome. It plays a significant role in maternal-fetal well-being and can affect complex pregnancy-related disorders such as HELLP Syndrome and pre-eclampsia (PE). Evidence continues to accumulate regarding the delicate balance of gut microbiota (GM) functions, including the potential role in immunologic conditions such as immune thrombocytopenic purpura, where the microbiota may influence platelet dynamics. The oral and placental microbiomes are also more similar to each other than the gut microbiome, highlighting distinct microbial influences during pregnancy. While we cannot wholly discount the relationship between microbiota and miscarriage, there is an increasing body of evidence to suggest that microbiota perturbations may have an indirect role in conditions like PE and HELLP syndrome, which can lead to adverse pregnancy outcomes. One way to support this frame is by considering the use of microbiome manipulation as a potential transformational approach to prenatal care research. This review examines these connections and highlights how manipulating the microbiome may open new avenues of therapy for these serious complications.</p> Graphical abstract <p></p>