In order to cope with the adverse effects of salt stress on plant growth and development, plants have evolved several ion transporters (such as high-affinity potassium transporter 1 HKT1 and Na+/H+ antiporter NHXs) to regulate ion balance under salt stress. Identifying regulators of these ion transporters is essential for elucidating plant salt stress response mechanisms and facilitating the development of salt-tolerant crops. In this study, we identified the pumpkin bax inhibitor-1 like (CmoBI1L), which localizes at the endoplasmic reticulum and stabilizes Na+ transporters CmoHKT1;1 and CmoNHX4 through protein-protein interaction assays and in vivo protein degradation assays. Knockout of CmoBI1L reduces the salt tolerance of pumpkin seedlings while overexpression of CmoBI1L enhances the salt tolerance through maintaining the ROS balance and photosynthetic capacity, as well as limiting Na+ transport from the root to the shoot. RNA-seq analysis indicated that CmoBI1L modulates ROS homeostasis and chlorophyll biosynthesis, highlighting its multifaceted regulatory roles. These findings provide new insights into the salt tolerance of pumpkin and offer a basis for developing salt-tolerant pumpkin germplasms.