Postbiotics are attractive as alternatives to antibiotics for use against post-weaning diarrhea. However, their beneficial mechanisms are largely unknown. In the current study, we first demonstrated that supplementation with 0.5% Pichia kudriavzevii FZ12 postbiotics in the diet significantly reduced diarrhea incidence, promoted growth performance, improved gut health performance, and significantly enriched beneficial bacteria, particularly Lactobacillus spp., in the intestines of weaned piglets. Importantly, we identified a heat- and proteinase K-sensitive component, cytochrome c, of the postbiotics that significantly promoted the growth and biofilm formation of Limosilactobacillus reuteri FP13. We demonstrated the importance of P. kudriavzevii FZ12 postbiotics in improving the intestinal health of a model animal and revealed that cytochrome c is one of the important components of yeast postbiotics. These findings may provide new insights into microbe-postbiotics interplay that can be applied to guidelines for dietary modulation to alleviate weaning-induced diarrhea.