Modified electroconvulsive therapy (MECT) is an effective treatment for mood and psychiatric disorders and provides rapid and significant improvements in severe symptoms of several mental health conditions. The basis and molecular mechanisms underlying the therapeutic effects of MECT are poorly understood. We attempted to compare the urinary proteome of each depressive patient before and after electroconvulsive therapy. 54 urinary proteomes from 9 patients were analyzed, including before and after MECT. Due to the heterogeneity of depression disorder, comparing the urine proteome of each person before and after treatment was used. Common differential protein and biological process were thought to contribute most to the changes caused by MECT. The common biological processes enriched by differential proteins through GO analysis with most patients mainly included cell adhesion (9/9 patients), immune response (7/9), axon guidance (7/9), and oxidation stress (7/9). Moreover, the common biological pathways identified by Ingenuity Pathway Analysis software showed that acute phase response signaling (7/9 patients), NRF2-mediated oxidative stress response (7/9), synaptogenesis signaling pathway (5/9), and ephrin B signaling (5/9) were all upregulated among each patient and were involved in promoting synaptic plasticity and neuroplasticity. Common biological processes and pathways top distributed in urine were reported about resulting in increased excitatory synaptic activity, which were related to the mechanism of MECT in the treatment of mental illnesses. In addition, the common differential proteins CSPG4, CBG, APP, NCAM1, and ARSA were suspected to be related to memory loss, memory damage, and memory formation, which might be the effects of MECT.