Zinc is an essential nutrient with important biological functions, and its deficiency can lead to several diseases. The zinc transporter families, ZIP and ZNT, play essential roles in regulating zinc homeostasis and dynamics in the body and cells. Specifically, ZIP4 is the primary zinc transporter responsible for zinc absorption in the small intestine. Previous studies have shown that Panax ginseng (P. ginseng) extract can promote mouse Zip4 expression, and ginsenosides, including Rc and Re, enhance zinc uptake. However, the effects of other metabolites present in P. ginseng extract remain unclear. Therefore, we fractionated P. ginseng extract using chloroform, ethyl acetate, and n-butyl alcohol, and evaluated the effect of each fraction on zinc uptake using mouse Hepa and Hepa/MRE-Luc cells that stably expressed luciferase under the promoter of metal-responsive elements. Luciferase activity assays demonstrated that the chloroform (F1), ethyl acetate (F2), and n-butyl alcohol (F3) fractions increased cellular zinc uptake. In particular, F1 fraction was found to induce Zip4 mRNA and protein expressions, which significantly enhanced zinc uptake. Ginsenosides were mainly present in the F2 and F3 fractions, indicating that metabolites other than ginsenosides in the F1 fraction would enhance zinc uptake by inducing Zip4 mRNA and protein expressions. Our study offers novel insights into the molecular mechanisms underlying zinc uptake by P. ginseng.