Objective: To analyze changes in liver and kidney function and lipid metabolism in patients with refractory nephrotic syndrome (RNS) after receiving different treatments. Methods: A total of 64 patients treated in the Wuwei Hospital of Traditional Chinese Medicine from January 2018 to January 2021 were included in this study. All subjects were diagnosed with RNS and randomly assigned to groups: a control group (32 cases) and an observation group (32 cases). The control group received cyclophosphamide + glucocorticoids, while the observation group received tacrolimus + glucocorticoids, both for six months. The various indicators of the two groups were compared. Results: After six months of treatment, the overall clinical efficacy rate of the observation group was significantly higher than that of the control group. Six months post-treatment, levels of serum ALT, AST, BUN, SCr, 24 h UTP, TG, and TC were reduced in both groups compared to baseline levels, with reductions more pronounced in the observation group. Serum ALB levels increased in both groups, with a more significant increase in the observation group. Statistical analysis showed these differences were significant (P < 0.05). There were no significant changes in FBG levels in either group (P > 0.05). Conclusion: For RNS patients, treatment with tacrolimus combined with glucocorticoids significantly reduces liver function damage, improves kidney function and lipid metabolism, and enhances clinical efficacy.