Objective: This study aimed to evaluate the effects of selenium-enriched yeast on the quality of coix seed jiulao. Methods: The coix seed was used as raw material, which was inoculated with selenium-rich saccharomyces cerevisiae to prepare coix seed jiulao. The changes of physicochemical properties, plant active components and in vitro antioxidant activity were measured during the fermentation of jiulao. Results: Compared with the S. cerevisiae group, the selenium-enriched S. cerevisiae group enhanced the improvement rate of alcohol content. It also accelerated the decrease rate of pH and total sugar content in the middle stage (12~30 h) of coix seed jiulao fermentation. After 36 h fermentation, the contents of total flavonoids and total polyphenols in the selenium-enriched S. cerevisiae group were increased by 14.43% and 9.77%, respectively, compared with S. cerevisiae group. In addition, after 36 h fermentation, the selenium content in S. cerevisiae group was only 0.007 μg/mL, while the selenium content of selenium-enriched S. cerevisiae group could reach 20.53 μg/mL, and the DPPH free radical scavenging rate and lipid peroxidation inhibition rate of coix seed jiulao were increased to 67.37% and 79.52%, respectively. Conclusion: Using selenium-enriched yeast to ferment coix seed jiulao can increase the selenium content of jiulao and improve the in vitro antioxidant activity and the quality of coix seed jiulao.