Objective To investigate the anti-fatigue effect of compound aqueous extracts of Ginseng Radix et Rhizoma, Polygonati Rhizoma, Polygonati Odorati Rhizoma, and Citri Reticulatae Pericarpium in mice.Methods The experiment included a blank control group, a positive control group (Rhodiola rosea capsules, 0.70 g/kg), and low, medium, and high dose groups of compound ginseng aqueous extracts (1.56, 3.30, and 6.60 g/kg, respectively), which were administered by gavage for 30 days. The anti-fatigue effect was evaluated using the weight-bearing exhaustion swimming test and by measuring biochemical markers, including hepatic glycogen, blood lactate, and blood urea nitrogen.Results Compared with the blank control group, the compound ginseng aqueous extracts had no significant effect on the normal weight gain or mental state of the mice (P>0.05). The medium and high dose groups significantly prolonged the swimming time during weight-bearing exhaustion (P<0.05). The high dose group significantly increased hepatic glycogen levels (P<0.05) and reduced blood lactate, blood urea nitrogen, and malondialdehyde levels (P<0.05).Conclusion The compound ginseng aqueous extracts help alleviate exercise-induced fatigue in mice and demonstrate strong anti-fatigue effect.