BCS III drugs exhibit high solubility and low permeability, and some excipients were reported to increase their permeability. Although some permeability-enhancing excipients were investigated, permeability-enhancing strategy still need to be improved. Firstly, we established a database and analyzed the possible effects of excipients. Sodium lauryl sulfate (SLS) was found to be the most-used permeability-enhancing excipients. Moreover, the quantitative models for predicting P and P of BCS III drugs with SLS were developed, and statistically meaningful descriptors include molecular weight (MW), pKa, logP, solubility, hydrogen bond (HB) count, rotatable bond count (RBC), and topological polar surface area. The models demonstrated a good fit and effective predictive capability with all the correlation R values over 0.7. Hydrogen bonding remains the most significant factor in enhancing drug permeability with SLS, while hydrophilicity is also vital in this process. It was also found that MW, logP, pKa, and RBC play significant roles in paracellular transport. In summary, current research did the systematic and quantitative analysis of BCS III drugs and their excipients, which may accelerate formulation research on BCS III products.