Background and Objectives: Persons with epilepsy (PwE) have a higher risk of developing psychiatric comorbidities compared with the general population. There is limited knowledge about the prevalence of multiple psychiatric conditions in PwE. We summarize the current evidence on the prevalence of multipsychiatric comorbidities in PwE compared with persons without epilepsy., Methods: A systematic review of multipsychiatric comorbidities in PwE compared with persons without epilepsy was performed, and the results were reported using the Preferred Reporting Items of Systematic Reviews and Meta-analyses reporting standards. The search was conducted from January 1945 to June 2023 in Ovid MEDLINE. Embase, and PsycINFO, using the search terms related to "epilepsy," "psychiatric comorbidity," and "multimorbidity," combined with psychiatric disorders. Abstracts were reviewed in duplicate, and data were independently extracted using standard proforma. Data describing multipsychiatric comorbidities in PwE compared with persons without epilepsy were recorded. Descriptive statistics and, when feasible, meta-analyses are presented. The risk of bias of the studies was assessed using the Newcastle-Ottawa Scale and the International League Against Epilepsy tool., Results: A total of 12,841 records were identified from the systematic database search, and 15 studies met the eligibility criteria. All included studies were deemed high-quality in risk of bias according to both tools. The prevalence of multipsychiatric comorbidity was greater in persons with compared with those without epilepsy. The pooled prevalence of concomitant depression and anxiety disorder in PwE in 2 population-based studies was 15 of 163 (9.2%), which was significantly higher than 250 of 10,551 (2.4%) in patients without epilepsy (odds ratio [OR] 3.7, 95% CI 2.1-6.5, p -value <0.001, I 2 = 0%, Cochran Q p -value for heterogeneity = 0.84). In 2 hospital-based studies, the prevalence of concomitant depression and attention-deficit/hyperactivity disorder in PwE (14/97, 14.4%) was significantly higher than in patients without epilepsy (5/126, 3.9%), with an OR 5.2 (95% CI 1.8-15.0, p -value = 0.002, I 2 = 0%, Cochran Q p -value for heterogeneity = 0.79)., Discussion: PwE experience elevated levels of multipsychiatric comorbidity compared with those without epilepsy. However, very few studies have empirically evaluated the extent of multipsychiatric comorbidity in PwE compared with persons without epilepsy nor their associations and consequences to prognosis in PwE.