Yupingfeng powder (YPFP), also known as Yupingfeng San, is a traditional Chinese medicine (TCM) formula comprising Astragali Radix, Saposhnikoviae Radix, and Atractylodis Macrocephalae Rhizoma, and is used clinically to treat renal diseases in China. Chemical metabolites in YPFP play a significant role in specific pathophysiologic mechanisms of renal diseases. Chemical metabolites, clinical application, and pharmacology of YPFP were comprehensively summarized. YPFP and its bioactive metabolites (notably flavonoids, saponins, polysaccharides, organic acids, lactones, coumarins) demonstrate significant pharmacological activities in renal diseases, including anti-fibrosis, antioxidant, immunomodulatory, anti-apoptosis, anti-inflammatory, and anti-ferroptosis. These activities alleviate symptoms and delay disease progression. Over recent decades, extensive research has confirmed the therapeutic benefits of YPFP and its bioactive metabolites in the medical intervention of renal diseases. This review systematically investigates the renoprotective effects of YPFP, including its therapeutic effect and multi-target mechanisms, providing a reference for the therapy of renal diseases.