Disintegration characteristics of red-bed mudstone pose a serious threat to the construction, management, and maintenance of engineering works in red-bed areas. To better understand these characteristics, naturally air-dried red-bed mudstone from the Lanzhou area of Gansu Province was selected as the research object. Indoor disintegration cycle tests were carried out under three conditions: combined dry-wet and cold-hot cycles, dry-wet cycles alone, and cold-hot cycles alone. At the end of each cycle, the samples were sieved to obtain the particle mass of each size fraction. On this basis, fractal theory was applied to calculate the grain-size fractal dimension during the disintegration process, thereby determining the fractal dimension at which the disintegration of red-bed mudstone tends to stabilize. The results showed that under the same water content and the same number of disintegration cycles, the combined dry-wet and cold-hot group exhibited the most severe disintegration, followed by the dry-wet cycle group, whereas the cold-hot cycle group showed no disintegration. With increasing water content, the particle mass of each size fraction of disintegrated red-bed mudstone exhibited four types of variation patterns, and the disintegration process underwent an abrupt acceleration when the water content reached 30%?40%. With an increasing number of disintegration cycles, the disintegration process of red-bed mudstone tended to cease when the grain-size fractal dimension reached 2.7?2.8.