Dietary supplementation with complex carbohydrates is known to alter the composition of gut microbiota, and optimal implementation of the use of these so called “prebiotics” could be of great potential in prevention and possibly treatment of obesity and associated cardiometabolic and inflammatory diseases via changes in the gut microbiota. An alternative to this “microbiocentric view” is the idea that health-promoting effects of certain complex carbohydrates reside in the host, and could secondarily affect the diversity and abundance of gut microbiota. To circumvent this potential interpretational problem, we aimed at providing an overview about whether and how dietary supplementation of different complex carbohydrates changes the gut microbiome in healthy non-obese individuals. We then reviewed whether the reported changes in gut bacterial members found to be established by complex carbohydrates would benefit or harm the cardiometabolic and immunological health of the host taking into account the alterations in the microbiome composition and abundance known to be associated with obesity and its associated disorders. By combining these research areas, we aimed to give a better insight into the potential of (foods containing) complex carbohydrates in the treatment and prevention of above-mentioned diseases. We conclude that supplemental complex carbohydrates that increase Bifidobacteria and Lactobacilli, without increasing the deleterious Bacteroides, are most likely promoting cardiometabolic and immunological health in obese subjects. Because certain complex carbohydrates also affect the host’s immunity directly, it is likely that host–microbiome interactions in determination of health and disease characteristics are indeed bidirectional. Overall, this review article shows that whereas it is relatively clear in which direction supplemental fermentable carbohydrates can alter the gut microbiome, the relevance of these changes regarding health remains controversial. Future research should take into account the different causes of obesity and its adverse health conditions, which in turn have drastic effects on the microbiome balance.