The fragmental disintegration processes of strongly weathered mudstone subjected to periodic changes in wet-dry state detrimentally affect numerous slope stability. To quantitatively study the disintegrating characteristics, laboratory-based eleven-cycle’s disintegration tests were performed on the mudstone samples taken from Guandukou area in Three Gorges region. Under the periodic action of wet-dry cycle, the tested mudstone samples continuously disintegrate, with bigger pieces with various sizes broken down into smaller fragments of different sizes. The fragmental disintegration process of the tested mudstone is relatively strong, but which cannot be indicated only by the content variation of small particles with some sizes (< 2 mm). To better characterize the slaking behavior, a quantitative measure based on the particle grading characteristics was proposed, with its effectiveness and reliability demonstrated by sensitive analysis. When the number of wet-dry cycles rises, the proposed slaking durability parameter decreases linearly while disintegration ratio shows slowly increasing tendency, indicating non-stop of mudstone disintegration subjected to cyclic changes in wet-dry state.