More than 57% of US adults take dietary supplements with the most common being daily multivitamins. Daily multivitamins are typically formulated in a pill or tablet form, however new options using a powder form to be mixed with diluent (water) are being utilized to increase bioavailability. While limited data is available, the theory is that multivitamins tablets must be adequately dissolved before entering the small intestine for assimilation, while powders come pre-dissolved before consumption and theoretically ensures enhanced bioavailability. Our aim was to investigate the bioaccessibility and bioavailability of minerals [magnesium (Mg), zinc (Zn), calcium (Ca), and potassium (K)] using a novel Foundational Nutrition supplement called AG1 compared to a tablet multivitamin. AG1 contains vitamins and minerals comparable to multivitamin tablets, but also includes prebiotics, probiotics, and phytonutrients. We employed the adapted Simulator of Human Intestinal Microbial Ecosystem (SHIME®) model to assess bioavailability and bioaccessibility of the study products using a simulated stomach and small intestine physiological environment equipped with a dialysis membrane (methylcellulose) to emulate absorption. Luminal contents were collected at the end of the stomach, duodenum, and 1-, 2-, and 3-hours after small intestine absorption simulation (dialysis) to assess bioaccessibility. The dialysis solution was measured at 1-, 2-, and 3-hours to assess bioavailability. A significantly higher (p < 0.05) percentage of the total amount of all minerals given at baseline was present at the end of the stomach and duodenum portion for the powder form vs. the tablet. There was a significantly higher % concentration_maximum (C_max) for Mg, Ca, and Zn for AG1 vs. tablet. Similarly, Mg, Ca, and Zn were more bioavailable but only Ca and Zn were more bioaccessible for AG1 compared to tablet. These preclinical data demonstrate that a greater proportion of minerals in AG1 enter the small intestine, have a higher C_max, and several are more bioaccessible and bioavailable than a tablet multivitamin in vitro.