BACKGROUND: There is a growing interest in the role of immune and inflammatory responses in mental disorders (MDs). Mean platelet volume (MPV) is an extensively utilized hemogram parameter that reflects systemic inflammation and immune function. Our research sought to determine whether a connection exists between MPV and various types of MDs. METHODS: We searched PubMed, EMBASE, PsychINFO, and Web of Science for eligible studies from inception to 15 February 2023, supplemented by manual searching the references from relevant articles. We applied standardized mean difference (SMD) and its 95% confidence interval (CI) to estimate the differences in MPV values in patients with MDs compared to controls. RESULTS: We analyzed data from 24 surveys with 4843 participants (2450 patients with MDs and 2393 healthy controls). Two-step meta-analyses were conducted to estimate the SMD in MPV value between individuals with and without MDs. Higher MPV values were substantially linked to MDs (i.e., depression, anxiety, bipolar disorder, and schizophrenia). Moderator and stratified analyses revealed that the aggregate effects were more robust in specific populations, such as younger patients and those who had not taken antipsychotic medication within the previous month. CONCLUSIONS: Our findings corroborate the role of inflammatory response in the pathogenesis of MDs and the pharmacological treatment of these conditions. Regarding the considerable heterogeneity among studies, the level of evidence was very low to moderate.