The invention discloses a quinoa saponin and wild chrysanthemum flower composition as well as a preparation method and application thereof, and relates to the technical field of medicines and foods. The quinoa saponin and wild chrysanthemum flower composition comprises the following components in parts by weight: 69.82-70.02 parts of a quinoa total saponin extract and 29.08-30.18 parts of a wild chrysanthemum flower extract, and 10% of pregelatinized starch is supplemented. The preparation method comprises the steps of raw material drying, saponin extraction, wild chrysanthemum flower extraction, organic extraction, purification, elution, rotary evaporation concentration, vacuum drying and particle preparation. Prepared quinoa saponin and wild chrysanthemum flower composition particles have good application prospects in the aspect of intestinal disease prevention and treatment. Quinoa bran is extracted and processed, ultrasonic-assisted ionic liquid is used for extracting quinoa saponin from the quinoa bran, reutilization of the quinoa bran is achieved, the extraction time is shortened, the quinoa saponin extract and the wild chrysanthemum flower extract are combined to be made into the medicinal granules, colibacillosis can be effectively prevented and treated, and the composition has good economic benefits and practical significance.