Objective To investigate the effects of lysiinositol B12, calcium carbonate D3 combined with recombinant human growth hormone (rhGH) on growth development and bone metabolism in children with short stature. Methods Seventy-eight cases of children with short stature admitted to Henan Zhengzhou Jinshui District General Hospital between January 2020 and March 2023 were selected, and the children were divided into a control group and a treatment group using the digital randomization table method, with 39 cases in each group. The control group was treated with rhGH only, and the treatment group was treated with lysiinositol B12 and calcium carbonate D3 on the basis of the control group. The growth and development status (height, weight, bone age, bone mineral density), and the related hormone levels [insulin growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), ghrelin], bone metabolism indexes [bone alkaline phosphatase (BAP), osteocalcin (OC), 25-hydroxyvitamin D (25-(OH)D)], and thyroid function [thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4)] of the two groups were recorded before and after the treatment, the occurrence of adverse reactions in the two groups was recorded and counted during the treatment process, and the parental satisfaction with the treatment effect was counted after the treatment using a satisfaction questionnaire developed by the hospital. Results After treatment, the growth and development status of both groups were better than those before treatment (P<0.05), and the height, weight, bone age, and bone mineral density of the treatment group were higher than those of the control group (P<0.05). After treatment, the levels of IGF-1 and IGFBP-3 were higher than those before treatment, and the level of ghrelin was lower than that before treatment (P<0.05); IGF-1 and IGFBP-3 levels in treatment group were higher than those in control group, while ghrelin levels were lower than those of the control group (P<0.05). After treatment, BAP, OC, 25-(OH)D levels of both groups were higher than those before treatment (P<0.05), the levels of BAP, OC and 25-(OH)D in treatment group were higher than those in control group (P<0.05). There were no significant differences between the two groups in thyroid function and adverse drug reactions after treatment(P >0.05). After treatment, parental satisfaction was 92.31%(36/39) higher in the treatment group than that of 71.79%(28/39) in the control group (P<0.05). Conclusion Calcium carbonate D3, lysiinositol B12 combined with rhGH has a good therapeutic effect on short stature, which can improve the level of bone metabolism and IGF-1 and other related hormones, and has no obvious adverse effects on thyroid function. It is safe and reliable, worthy of clinical promotion and application.