We describe here a theoretical framework to model the bulk degradation of hydrogels, which are prepared by chemical cross-linking of pendant functional groups on long polymer chains. The random order of the cleavage of degradable bonds was described by stochastic Monte Carlo simulation. The events of bond cleavage were related to the macroscopic changes of hydrogel by the Bray-Merrill equation. Next, the time for the gel to disintegrate was predicted by considering the relation between the recursive nature in breaking the cross-link nodes and gel-to-sol transition. To start the simulation, initial network properties including the number of active functional groups on the polymer chain and the concentration of polymer were employed as input, and the kinetic rate constant of bond cleavage was fitted for the swelling profile. No fitting parameter was required for disintegration time. A series of degradable hydrogels composed of dextran modified by methacrylate and thiol groups were synthesized and examined experimentally to verify the models. The measured mass swelling ratio and gel disintegration time matched with the model predictions. Correlation was found between the initial hydrogel network properties and the profiles of degradation. The results also revealed that degradable hydrogels with a wide range of disintegration times (from 3 days to 1 month) could be prepared by manipulating the hydrogel formulation (for example, polymer concentration and degree of modification) without altering the chemistry of the cleavable bond.