Excess nutrient uptake is one of the main factors of complications related to metabolism disorders. Therefore, efforts have emerged to modulate nutrient transport in the intestine. However, current approaches are mainly invasive interventions with various side effects. Here, a pH-responsive
hydrogel is formulated by acidifying the
hydroxide compounds within
sucralfate to allow electrostatic interactions between
pectin and
aluminum ions. The pH responsiveness relies on the alternation of
cations and
hydroxide species, providing reversible shifting from a
hydrogel to a complex coacervate system. It acts as a transient physical barrier coating to inhibit intestinal absorption and changes the viscosity and barrier function in different parts of the gastrointestinal tract, showing enhanced mucoadhesive properties. The therapeutic
hydrogel remarkably lowers the immediate
blood glucose response by modulating nutrient contact with bowel mucosa, suggesting potential in treating diabetes. In addition, it significantly reduces
weight gain, fat accumulation, and hepatic
lipid deposition in rodent models. This study provides a novel strategy for fabricating pH-responsive
hydrogels, which may serve as a competent candidate for metabolism disorder management.