Abstract： Objective： To observe the clinical effect of Jianpi Bushen Prescription combined with western medicine in treating idiopathic short stature （ISS） with spleen and kidney deficiency syndrome and its effects on the growth hormone-releasing hormone （GHRH）/growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis. Methods： A total of 98 cases of children with ISS with spleen and kidney deficiency syndrome treated in the Department of Chinese Medicine Pediatrics at Lanxi People's Hospital from January to December 2023，were selected and randomly divided into the conventional group and the comprehensive group using the simple random method，with 49 cases in each group. The conventional group was treated with Recombinant Human Growth Hormone combined with Lysine Inositol and Vitamin B12，and the comprehensive group was additionally treated with Jianpi Bushen Prescription based on the treatment of the conventional group. Both groups were treated continuously for six months. The height， weight， bone age， predicted height， traditional Chinese medicine （TCM） syndrome scores， and levels of Klotho protein，bone alkaline phosphatase （BAP），GH，IGF-1，insulin-like growth factor-binding protein 3 （IGFBP-3）， and GHRH in the two groups were compared before and after treatment. Adverse reactions in both groups were recorded. Results：After treatment，the height，weight，bone age，and predicted height in the two groups were increased when compared with those before treatment （P＜0.05）， with the comprehensive group showing greater improvements in height，weight，and predicted height than the conventional group （P＜0.05）. TCM syndrome scores in the two groups were decreased when compared with those before treatment （P＜0.05）， with the comprehensive group showing lower scores than the conventional group （P＜0.05）. The levels of Klotho protein， BAP， GH， IGF-1， IGFBP-3， and GHRH in the two groups were increased when compared with those before treatment （P＜0.05）， with the comprehensive group showing higher levels than the conventional group （P＜0.05）. There was no significant difference being found in the comparison of the incidence of adverse reactions between the two groups （P＞0.05）. Conclusion： Jianpi Bushen Prescription combined with western medicine for ISS with spleen and kidney deficiency syndrome can improve the secretion of GH and bone metabolism and promote the growth and development of children，with good safety.