The epidemic of obesity and metabolic syndrome is a major public health concern internationally. There is increasing knowledge and research in areas of appetite regulation and drivers of obesity but there is still a gap on how the interactomes are altered in a metabolically dysregulated human body. The human microbiome has been implicated in the pathogenesis of obesity. While the association of gut bacteriome dysbiosis is well described in obesity and metabolic syndrome, there is a lack of an integrative understanding about the roles of the non-bacterial microbiome (virome, mycobiome, and archaeome) in the pathogenesis and protection of obesity and metabolic syndrome. Accumulating studies have revealed that the non-bacterial microbes in the gut, including viruses/phages, fungi, and archaea, are profoundly altered in obesity, and impact host adiposity and physiology in nuanced manners. In this review, we aim to provide a comprehensive view on the role and the mechanisms of the gut virome, mycobiome, and archaeome in obesity. These insights will shed light on the translational value as well as the future research directions for harnessing the gut non-bacterial microbial entities in the therapeutics and prevention of metabolic diseases.