Objective To explore the differences of traditional Chinese medicine (TCM) syndromes, clinical symptoms and brain-gut peptide level between middle-aged and elderly patients with young patients with postprandial distress syndrome (PDS). Methods A total of 65 PDS patients admitted to our Acupuncture Department from March to October 2018 were enrolled in this study, and divided into the middle-aged and elderly group (>45 years old) and the young group (≤45 years old). The 2 groups of patients were classified according to TCM syndrome differentiation. The severities of dyspepsia, quality of life, anxiety and depression were evaluated by symptom index of dyspepsia (SID), Nepean dyspepsia index (NDI) and hospital anxiety and depression scale (HADS), respectively. The plasma levels of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), ghrelin and substance P (SP) were measured by enzyme-linked immunosorbent assay (ELISA). The data was analyzed using SPSS statistics 20.0. Depending on the types of data, independent sample t test, Mann-Whitney U test, or Chi-square test was used for comparison between 2 groups. Results There was no significant differences in the compositions of liver-stomach disharmony syndrome, spleen-stomach weakness syndrome and spleen-stomach dampness-heat syndrome between the 2 groups (Chi-square=4.787, P=0.091). The score of epigatric burning symptom was significantly higher in the middle-aged and elderly group than the young group [1(0,1) vs 0(0,1), P<0.05], but no such differences were seen in the other symptoms, and scores of NDI and HADS between them (P>0.05). The plasma level of CGRP was significantly higher in the middle-aged and elderly group than the young group [(1.06±0.24) vs(0.93±0.25)ng/ml, P<0.05], but there was no significant differences in the levels of VIP, SP and ghrelin between the 2 groups (P>0.05). Conclusion The middle-aged and elderly PDS patients experience severe epigastric burning symptom, and have significantly increased[JP+2]plasma CGRP level, which may be associated with ageing-related decreased gastrointestinal motility and delayed gastrointestinal emptying.