This study aimed to investigate the alleviating effects and potential mechanisms of Glycyrrhiza polysaccharide (GP) on lipopolysaccharide (LPS)-induced immune stress in broiler chickens. A total of 240 one-day-old AA broiler chicks were randomly assigned to a 2×2 factorial design, comprising a control group and a GP group (diet supplemented with 1500 mg/kg GP). From day 10, birds were injected with either LPS or physiological saline to establish an immune stress model. The experiment was divided into three phases: the initial phase (days 1–10), the stress phase (days 10–28), and the recovery phase (days 28–35). The effects of GP intervention were systematically evaluated in terms of growth performance, immune organ indices, serum inflammatory cytokines, intestinal morphology, and goblet cell count. Furthermore, the underlying molecular mechanisms were explored through integrated transcriptomic and proteomic analyses of spleen tissue.