Depression is a common mental illness worldwide. Neuroimaging techniques, such as magnetic resonance imaging and functional magnetic resonance imaging, play an essential role in diagnosing and evaluating depression. This study is based on magnetic resonance imaging (MRI)-related research to explore the comparison of brain function and structure between patients with severe depression and normal individuals, and to conduct meta-analysis. We conducted searches in various databases such as PubMed, Web of Science, Embase, and Cochrane Library to obtain research data on comparing brain function and structure between patients with severe depression and healthy individuals. The search keywords included "Major Depressive Disorder", "Brain Function", "Brain Structure", "Depression", "MRI", and "Magnetic Resonance". The quality assessment was conducted using the bias risk assessment tool recommended by the Cochrane Collaborative Network. Literature was screened following the predetermined inclusion and exclusion criteria, and Anisotropic Effect-Size Seed-Based Differential Mapping (AES-SDM) was used for systematic meta-analysis. Regression analysis was performed on age, gender, disease duration, years of education, and treatment status. After a thorough screening process, 10 documents were selected for subsequent analysis. These studies consisted of 477 study subjects, including 231 depression patients and 246 healthy individuals. The proportion of women was 36%-75%, and the disease duration was 3-60 months. The patients in 4 documents had first attacks, and the patients in the other 6 documents had multiple attacks. The baseline conditions of the 10 included documents were consistent and comparable. None of the studies reported blinding methods, and none of the results had incomplete data. The Regional homogeneity (ReHo) levels in the left precuneus (BA7), lentiform nucleus (BA48), and left prefrontal lobe (BA32) were significantly increased in the depression group, with voxel numbers of 358, 116, and 181, respectively. Conversely, the left postcentral gyrus (BA4), left cerebellar area (hemispheric lobule I, IV/V, lingual gyrus, fusiform gyrus), left fusiform gyrus (BA30), and right cingulate gyrus (BA23) were significantly reduced, with voxel numbers of 17, 50, and 124, respectively. Furthermore, regression analysis showed that gender, age, disease duration, years of education, and disease severity were potential influencing factors, and the disease duration demonstrated the most significant impact on the left cingulate gyrus (SDM = 2.777). There are significant differences in brain function and structure between patients with major depression and healthy individuals. Furthermore, our findings reveal a substantial correlation between the severity of depressive symptoms and brain function and structure indicators. These findings provide novel research directions and ideas for the diagnosis and treatment of depression.