Comparing to males, females require much more morphine to produce comparable levels of analgesia, suggesting a difference in the endogenous hyperalgesia and analgesia modulation between sexes. Aside from hormones, emerging evidence suggests sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and American College of Gastroenterology (ACG), up to 25 % of the population having visceral pain at any one time, and in the United States 10-15 percent of adults suffering from irritable bowel syndrome (IBS). Here we analyzed literatures on clinical reports of sex differences in visceral pain focusing on IBS, other form of bowel dysfunction and comorbidities, and summarized animal models that provided means to investigate the underlying molecular mechanisms in sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems all contribute to sex-dependent nociception and nociplasticity in the painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.