Cancer-related fatigue is the most common complication in patients. Astragalus membranaceus is widely used in many countries to treat cancer, but its efficacy and safety is uncertain. This study aimed to summarize the evidence on Astragalus membranaceus on cancer-related fatigue and quality of life in patients with cancer. Nine electronic databases were explored for the clinical randomized controlled trial of intervention with Astragalus membranaceus alone for cancer-related fatigue and quality of life in cancer patients from inception to July 1, 2022. The risk of bias assessment tool was adopted by Cochrane Handbook 6.1.0. The effect size was estimated using relative risk and mean difference with a corresponding 95% confidence interval. Review Manager 5.4 was used for meta-analysis. The evidence level was assessed using Grading of Recommendation, Assessment, Development and Evaluation (GRADE). Eight studies were included. The results of the meta-analysis showed that the addition of Astragalus membranaceus to the control group was effective in reducing cancer-related fatigue (SMD = -1.63, 95% CI [-1.90, -1.36],  < .00001) and (RR = 1.55, 95% CI [1.19, 2.02],  = 0.001) in patients with cancer and improving quality of life (SMD = 0.86, 95% CI [0.17, 1.55],  = 0.01) and (RR = 1.57, 95% CI [1.10, 2.23],  = 0.01). The current evidence is supportive of the efficacy of Astragalus membranaceus in patients with cancer-relate fatigue and their quality of life, but due to the small and low quality of the included literature and the lack of uniformity in terms of cancer type as well as treatment modalities, there is currently insufficient evidence to provide strong support for the clinical use of Astragalus membranaceus in the treatment of cancer-related fatigue. More high-quality evidence is needed in the future to further validate the use of Astragalus membranaceus in the treatment of clinical cancer-related fatigue. A review protocol was developed and registered in the International Prospective Register of Systematic Reviews (PROSPERO). Registration number: CRD42023442277. Registered 20 July 2023.