Drug release in phosphate buffered saline (PBS pH 7.4) and artificial gastric juice (AGJ pH 1.2) and its relationship with kinetic and thermodynamic parameters of drug sorption onto soy protein (SP) fibers have been studied using Diclofenac, 5 Fluorouracil and Metformin as model drugs. Since SP is biodegradable, biocompatible, abundant and annually renewable, it has been widely used in medical applications. To understand drug release from SP fibers using sorption, kinetic and thermodynamic parameters have been investigated. Quantitative relationship between drug release and drug loading concentration, affinity, and activation energy for diffusion was established to predict initial bursts and later drug release. The study showed that Diclofenac had high initial bursts in PBS but more constant release in AGJ. It also has been found that drugs with lower diffusion coefficient and higher affinity (especially van der Waals force) on SP fiber are more suitable for sorption loading to achieve higher loading capacity and more constant releasing rate.