Background : Zinc (Zn) is one of dietary micronutrients and it is second highest trace element in the body. Over 95% of Zn is located in the cells, but its dominant storage site is absent in the body. Deficiency of Zn may result in anorexia, dysgeusia, dysosmia, skin rash, infection, alopecia, growth failure, and impaired wound healing. Therefore, adequate supplementation of Zn is very important to maintain normal physiological conditions. Methods and Results : Zinc sulfate monohydrate (ZnSO4)-loaded nanocomposites (NCs) were fabricated by using a hot-melt extruder (HME) system. Soluplus (SP) was adopted as an amphiphilic polymer matrix for HME processing. The micro-size of ZnSO4 dispersion was reduced to nano-size by HME processing with the use of SP. ZnSO4 could be homogeneously dispersed in SP through HME processing. ZnSO4/SP NCs with a 75 ㎚ mean diameter, a 0.1 polydispersity index, and a -1 mV zeta potential value were prepared. The physicochemical properties of ZnSO4/SP NCs and the existence of SP in ZnSO4/SP NCs were further investigated by solid-state studies. Nano-size range of ZnSO4/SP NC dispersion was maintained in the simulated gastrointestinal environments (pH 1.2 and 6.8 media). No severe toxicity in intestinal epithelium after oral administration of ZnSO4/SP NCs (at 100 ㎎/㎏ dose of ZnSO4, single dosing) was observed in rats. Conclusion : These results imply that developed ZnSO4/SP NC can be used as a promising nano-sized zinc supplement formulation. In addition, developed HME technology can be widely applied to fabricate nano formulations of inorganic materials.