The gut microbiome has been the subject of increasing interest as integral to our health. Few realize that the enormous benefits of vitamin D (VD) and magnesium (Mg) are highly dependent on a healthy gut microbiome. Short chain fatty acids, especially butyrate, reflect not only a healthy gut microbiome but also VD status. Suboptimal VD, Mg, or butyrate translates to some degree of gut dysbiosis and vice versa. Mg dependent secondary bile acids, indoles, and tryptophan, all microbial metabolites and longevity agents, are also discussed. Mg is indispensable to not only the synthesis of the active form of VD but also that of 7-dehydrocholesterol (7-DHC) from acetate. 7-DHC is the substrate for solar conversion to D3. The steadily increasing Ca:Mg in the Western diet and its troubling impact on parathormone (PTH) is discussed. Gut dysbiosis further complicates this. A model addressing the seemingly contradictory reports regarding calcium, magnesium, and VD efficacy among disparate groups is presented. Biochemical and physiologic interlinkages are legion and most remain hidden. This limited mini review exposes insight into the tight linkage between 25(OH) D3 and Ca:Mg, facilitated by the gut microbiome. A model incorporating the physiologically discordant but reinforcing effects on this linkage based on genes, culture, socioeconomic status, and diet is proposed.