BACKGROUND: Dyspepsia, characterized by symptoms in the gastroduodenal region, poses diagnostic challenges despite Rome IV criteria. AIM: This study aimed to investigate the prevalence of two underreported symptoms, Empty Stomach Sensation and Bothersome Hunger Sensation, in dyspeptic patients, and their association with the disorder of gut-brain interaction. METHODS: A cross-sectional study surveyed 1,211 individuals in northwest Mexico, assessing dyspeptic symptoms with pictograms and a 7-point Likert scale. Logistic regression analyzed associations between dyspepsia, Empty Stomach Sensation, and Bothersome Hunger Sensation. RESULTS: Dyspepsia prevalence was 39.1%, being overlap syndrome the most common (42.7%) phenotypic presentation. Empty Stomach Sensation prevalence in dyspeptic patients was 43.8% versus 12.6% in non-dyspeptics (p <
0.001). Bothersome Hunger Sensation prevalence in dyspeptics was 25.4% compared to 5.6% in non-dyspeptics (p <
0.001). Both symptoms were associated with epigastric pain syndrome, postprandial distress syndrome, overlap syndrome, anxiety disorders and other gastroduodenal symptoms. CONCLUSIONS: Empty Stomach Sensation and Bothersome Hunger Sensation, though prevalent in dyspeptic patients, are often overlooked. Strengths of this study include its large sample size and comprehensive assessment of symptoms. Limitations include the lack of diagnostic endoscopy and long-term follow-up. Future research should explore the underlying mechanisms of these symptoms and their implications for clinical management.