In this experiment, different probiotics were used to ferment quinoa straw feed to explore the optimal fermentation process of compound probiotics to ferment quinoa straw feed. In the experiment, Lactobacillus, Saccharomyces cerevisiae and Bacillus amyloliquefaciens were selected as fermentation agents, which were composed of Lactobacillus and Saccharomyces cerevisiae, Lactobacillus and Bacillus amyloliquefaciens in different proportions, and an orthogonal experiment with three factors and three levels was set up. Each compound agent fermented quinoa straw feed included 9 test groups, and a blank control group was set at the same time. The three factors in the test were the mixed bacteria ratio of quinoa straw feed fermentation, fermentation time and fermentation water content. The three levels were set as follows: the mixed bacteria ratio of 1∶1, 1∶2, 2∶1; fermentation water content of 50%, 60%, 70%, by setting short-term (3 d, 5 d, 7 d) and long-term (10 d, 20 d, 30 d) fermentation of quinoa straw, the nutritional indicators of quinoa straw after fermentation were detected in different test groups, the dominant fermentation strains and fermentation process of quinoa straw were determined, and the treatment was optimized by response surface method to obtain the optimal fermentation process. The test results showed that when the fermentation conditions were set at a water content of 60%, a fermentation time of 30 days, and a ratio of 1∶2 of Lactobacillus and Saccharomyces cerevisiae inoculants, the nutritional content of quinoa straw feed changed significantly. Long-term fermentation of quinoa straw feed by Lactobacillus and Saccharomyces cerevisiae had more significant benefits, and both short-term and long-term fermentation of quinoa straw feed by Lactobacillus and Bacillus amyloliquefaciens could promote it to a certain extent. In summary, the optimal fermentation process for quinoa straw feed was that the ratio of fermentation agents (Lactobacillus and Saccharomyces cerevisiae) was 1∶2, the water content was 60%, and the fermentation time was 30 days. At this time, the crude protein, crude fat, crude fiber, and crude ash contents of the quinoa straw feed were 14.68%, 3.67%, 24.37%, and 11.26% respectively, and the contents of crude protein, crude fat, crude fiber, and crude ash were 14.69%, 3.71%, 24.36%, 11.22% respectively after optimization by response surface methodology.