Infant formula (IF) based on cow milk and goat milk is a substitute food for infants who are underfed with human milk. In our previous study, we reported the composition and physicochemical stability of IF based on milk from cows and goats and a combination of both milks. Here, we investigated the effects of these 3 IFs on intestinal immunity and short-chain fatty acid production (SCFAs) using human microbiota-associated (HMA) mice and selected human milk as a positive control. The results showed that goat milk-based IF is associated with a functional immune advantage, due to the rise in the levels of immune-related cytokines interleukin (IL)-2 and IL-10, decreased levels of intestinal permeability markers D-lactic acid and endotoxin, and increased mRNA levels of intestinal tight junction proteins occludin and claudin. In addition, the intestine of mice fed with goat milk-based IF contained 12.06 μmol/g acetate, 2.42 μmol/g propionate, and 1.72 μmol/g butyrate, which reached 69%, 79%, and 60% of the levels in human milk, respectively. Our results indicate that goat milk-based IF improves intestinal immune function and promotes the production of intestinal SCFAs.