To improve the durability and bioavailability of alginate, a one-step extrusion method was successfully applied to prepare alginate/gelatin core-shell beads. Gelatin cross-linked with glutaraldehyde was used as the core, while sodium alginate was used as the shell. To evaluate the effect of the sodium alginate shell on the in vitro drug release properties of the beads for biomedical applications, two drug models were used: water-soluble metformin hydrochloride and water-insoluble indomethacin. The structure and properties of different core-shell beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and swelling tests. The results showed that the beads consist of obvious inner core and outer skin layer which coats the surface stably. In addition, the core-shell structure improved the thermal stability of the beads and the entrapment efficiency reached 90% with a sodium alginate shell. As demonstrated, there is a gradual decrease in the swelling degree as the GTA or alginate concentration increases. For indomethacin, the cumulative release was 8.7% after 360min in HCl buffer. The anomalous transport mechanism was the predominant factor affecting the release behavior of the metformin hydrochloride-loaded beads and indomethacin loaded beads were controlled by case-II transport. This work suggests that the core-shell structure could improve the swelling properties and drug release behavior of the beads.