Corn zein protein is a cheap, widely available biopolymer that is easily extracted from corn and processed into useful forms. In this study, zein was dissolved along with several model drugs or sodium citrate, which was then cast into thin films or air-spun into nanofibers. The molecular weight, solubility, and charge of the selected model drugs are different, and the weight percentage of citrate also varies (1%–30%). The integrity of the loaded biomaterials was characterized through FTIR, SEM, DSC, and TGA. Due to the high surface-area-to-volume ratio of nanofibers, FTIR analysis showed that the therapeutics strongly interacted with the protein structure of zein nanofibers, transforming their structure from a random coil network to a more ordered alpha helical structure. Zein films did not show this obvious shift. This structural change reflects the results of a drug release study where nanofibers showed a slower, sustained release of therapeutics compared with their film counterparts. Statistical analysis by t-test proved a significant difference in release from fibers vs. release from films (p < 0.01 for low wt%). The structural integration of zein with its therapeutics also improved the thermal properties of the biomaterial, where fibers did not degrade until temperatures reached 160 °C, but films degraded earlier at 130 °C. Finally, the biocompatibility of zein was confirmed by culturing HEK293 cells on different zein films and fibers for 72 h. An MTT assay confirmed good biocompatibility and an improved cell density on fibers and films compared with a blank control. These promising results, summarized in Figure 1, demonstrate that corn zein has a large potential in the field of drug delivery and biomaterials.