Growth stagnation or weight loss is prevalent in weaned piglets, with post-weaning diarrhea severely compromising intestinal health, underscoring the criticality of intestinal structural integrity for preventing digestive disorders. Tight junction proteins (TJPs), core components of intestinal intercellular junctions, play indispensable roles in maintaining barrier function, nutrient absorption, and intestinal homeostasis by regulating paracellular permeability and mediating immune defense-related signaling pathways. Dysregulated TJP expression disrupts these processes and impairs piglet growth performance. Despite recent progress in characterizing TJP-mediated regulation of intestinal health in weaned piglets, key knowledge gaps remain regarding the specific regulatory mechanisms by which distinct TJP subtypes modulate intestinal microbiota–immune crosstalk. Future research should prioritize elucidating the effects of nutritional interventions on TJP expression and intestinal health, as well as the molecular mechanisms underlying TJP involvement in intestinal diseases. These efforts will provide theoretical support for developing novel feed additives and nutritional strategies to improve weaned piglet health.