Background and Purpose Functional dyspepsia (FD) is a gastrointestinal disorder of unknown etiology. Although micro‐inflammation appears to be important in the pathogenesis, studies evaluating immune activation in FD have been inconsistent. A systematic review of literature and meta‐analysis was performed to compare immunologic cell counts and cytokine levels in the mucosa and peripheral blood of individuals with FD and healthy controls. PubMed, Embase, and the Cochrane library were searched. Data on immunologic cell counts and cytokines levels among individuals with FD and control groups were extracted and compared by calculating standard mean differences (SMD). Thirty‐seven studies met the inclusion criteria. Mast cell (SMD = 0.94, 95%CI 0.26‐1.62, P = .007) and eosinophil counts (SMD = 0.36, 95%CI 0.06‐0.68, P = .03) in the stomach were increased, among individuals with FD compared to controls. Similarly, mast cell (SMD = 0.66, 95%CI 0.20‐1.13, P = 0.005) and eosinophil (SMD = 0.95, 95%CI 0.66‐1.24; P < .001) counts in the duodenum were also increased in those with FD compared to controls. In a subgroup analysis, elevated eosinophil counts in the duodenum were observed in both post‐prandial distress syndrome (SMD = 0.97, 95%CI 0.46‐1.47, P = .0002) and epigastric pain syndrome subtypes (SMD = 1.16, 95%CI 0.48‐1.83, P = .0008). No differences in mucosal intraepithelial lymphocyte, enterochromaffin cell, and neutrophil counts, as well as, peripheral interlukin‐6 (IL‐6) and IL‐10 levels were observed among individuals with FD and controls. Micro‐inflammation in the form of local immune cell infiltration, particularly eosinophils and mast cells, characterizes the pathogenesis of FD. A systematic review and meta‐analysis of 37 studies evaluating peripheral and mucosal immune cytokines and cells were performed. Gastroduodenal eosinophils and mast cells were increased in individuals with FD compared to healthy controls.