Objective To explore the therapeutic effects of magnesium valproate plus lamotrigine in patients with mental disorders due to refractory epilepsy.Methods A total of 120 patients with mental disorders due to refractory epilepsy treated in the Xi'an North Hospital from January 2020 to January 2022 were included in this study. These patients were divided into control group （59 patients） and test group （61 patients）. The control group received magnesium valproate， and the test group received magnesium valproate plus lamotrigine. The two groups were compared for response rate and expression of interleukin-1β （IL-1β） and interleukin-6 （IL-6） in serum and tumor necrosis factor-α （TNF-α） and interleukin-2 （IL-2）IL-2 in peripheral blood.Results The overall response rate for epilepsy seizure was significantly higher in the test group than in the control group （93.4% vs 81.4%， P<0.05）. The overall response rate for mental disorders was significantly higher in the test group than in the control group （98.4% vs 72.9%， P<0.05）. At 1 month after treatment， the expression levels of IL-1β， IL-6， TNF-α， and IL-2 were significantly lower in the test group than in the control group （P<0.05）.Conclusions Magnesium valproate plus lamotrigine is effective in treating mental disorders due to refractory epilepsy and effectively regulates the expression of IL-1β and IL-6 in serum and IL-2 and TNF-α in peripheral blood.