The invention relates to a composition of 20(S)-protopanoxadiol and wolfberry polysaccharide with anti-fatigue effect and application thereof. Pharmacodynamics study discovers that the composition (codonopsis and lycli tablet) of the 20(S)-protopanoxadiol and the wolfberry polysaccharide in a certain ratio range has the remarkable anti-fatigue effect. Compared with a single medicament, the composition has synergistic effect. The composition matched with proper pharmaceutic and edible auxiliary materials can be applied to medicine and health care products.