Enzyme-induced carbonate precipitation (EICP) has emerged promising in various geotechnical applications, and has been presented as an alternative to the traditional cementitious materials-based ground improvement method. However, the study on mechanical properties and disintegration behavior of EICP-reinforced sea sand subjected to drying-wetting cycles are limited. This study investigated the mechanical properties and disintegration behavior of EICP-reinforced sea sand against the impact of drying-wetting (D-W) cycles. The uniaxial compressive strength (UCS) tests were performed to discuss the effect of drying-wetting cycles on the mechanical behavior of EICP-treated sea sand. The disintegration tests were conducted on EICP-treated sea sand to investigate the disintegration resistance of bio-cemented samples with various cementation levels. The microstructures of samples before and after disintegration were examined to disclose the disintegration mechanisms of EICP-reinforced sea sand. D-W cycles significantly affect the mechanical properties of EICP-reinforced sea sand, with UCS decreasing by 63.7% after undergoing 15 D-W cycles. The disintegration resistance index of specimens with a lower cementation level decreases significantly under the effect of D-W treatment. The higher disintegration resistance of specimens with higher cementation can be attributed to more crystals with better crystallinity formed in the contact point between sand particles within specimen. The crystals formed by soybean husk urease are mainly calcite and the crystallinity of spherical calcites would gradually change into larger rhombic calcite with further bio-grouting. The crystal with poor crystallinity is susceptible to the effect of D-W treatment, resulting in the obvious disintegration of EICP-reinforced sea sand. Overall, this study is expected to provide useful guidance on the long-term stability and drying-wetting disintegration mechanisms of EICP-reinforced sea sand.