Objective: To analyze the effect of mood stabilizer plus ziprasidone on the occurrence of agitation symptoms in patients with BD disease. Methods: 386 patients with BD admitted to our hospital from January 2022 to April 2024 were selected as the study objects. Patients were randomly divided into observation group and control group by envelope method, with 193 cases in each group. The control group was treated with sodium valproate combined with olanzapine. Observation group was treated with sodium valproate combined with ziprasidone. The severity of mania symptoms (BRMS, YMRS), agitation symptoms (CMAI), inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)] and serum serum neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA)] of the two groups were analyzed and compared. Results: After treatment, BRMS and YMRS scores in both groups were significantly lower than before treatment, and BRMS and YMRS scores in the observation group were significantly lower than those in the control group (P < 0.05). After treatment, the scores of verbal agitation, physical aggression and non-aggression in both groups were significantly lower than before treatment, and the scores of verbal agitation, physical aggression and non-aggression in the observation group were significantly lower than those in the control group (P < 0.05). After treatment, TNF-α, IL-1β, 5-HT and DA in both groups were significantly lower than before treatment, and TNF-α, IL-1β, 5-HT and DA in observation group were significantly lower than those in control group (P < 0.05). Conclusion: Treating BD patients with mood stabilizer combined with ziprasidone can effectively control mania, reduce agitated behavior, regulate inflammatory response and neurotransmitter secretion.