The effects of two cross-linking agents (genipin and polyphenol) on the physical properties of gelatin hydrogels were studied to determine the more effective natural cross-linking agent. The highest gel strength obtained with polyphenols was 136.9 N/mm2 at concentrations up to 360 μg polyphenols/g gelatin, whereas the highest strength of samples cross-linked with genipin was 98.4 N/mm2 with 300 mg genipin/g dry gelatin. Scanning electron microscopy showed that gelatin modified by polyphenols at 360 μg/g gelatin had the most compact surface. Cross-linked gelatin-polyphenol exhibited a markedly enhanced denaturation temperature and greater thermal stability than gelatin–genipin.