BACKGROUND The thickness of the alveolar mucosa influences the probability of the occurrence of denture-induced irritations. Thick denture-supporting tissues offer relief from mucosal tenderness and ulcers; however, the uniformity of the thickness across the entire mandibular alveolar mucosa cannot be accurately determined in edentulous patients. This study aimed to assess the mucosal thickness of the denture-bearing area in the edentulous mandible. METHODS Twenty-seven edentulous patients underwent cone-beam computed tomography scanning, wherein the patients wore a record base to retract soft tissues away from the alveolar mucosa. The measured regions were the central incisor (IC), lateral incisor (IL), canine (Ca), first premolar (P1), second premolar (P2), first molar (M1), and second molar (M2) regions. The thickness was measured in the alveolar ridge crest (T), buccal (B1-B4), and lingual (L1-L4) alveolar ridge mucosa. The average thickness of the mucosa at buccal sides (B) and lingual sides (L) were also assessed. RESULTS The differences in the mucosal thickness between the left and right sides were not significant. In the Ca-M2 regions, T was the thickest, and L3 was the thinnest of all the measured points in the same regions. L was significantly less than B in posterior regions (P < 0.01). On the other hand, M2 at L4 was thinnest of all the measured regions from Ca to M2 (P < 0.01), and was thicker than IC, IL, P1, and P2 at B2. CONCLUSIONS Since the mucosal thickness of denture-bearing area in the edentulous mandible is not uniform; the tissue surface of the denture base or custom tray should be selectively relieved, which may reduce the risk of denture-induced irritations.