Uranium poisoning is increasingly recognized as a public health issue. Polygonatum kingianum (PK) is valued for its therapeutic properties and food applications. Original research showed PK aqueous extract (PKAE) and polysaccharides (PKP) could alleviate uranium-induced cytotoxicity in vitro. Assessing the combined therapeutic potential of PKP with other components is crucial. The study examines the efficacy and mechanisms of PKP, saponins (PKS) and PKP + PKS to treat uranium-induced kidney damage in rats by analyzing alterations in blood and urine biochemical indices, apoptotic protein expression, and uranium accumulation. The poisoning led to a substantial decrease in renal superoxide dismutase, glutathione levels, and total antioxidant capacity, coupled with a notable increase in malondialdehyde, urea, uric acid, creatinine, and total oxidative status. However, these detrimental changes were mitigated by treatments with PKAE, PKP, PKS, and PKP + PKS, which also effectively reduced uranium accumulation in the rat kidneys. Compared to the uranium model group, the treatment groups increased the expression of Bcl-2 and Nrf2, while down-regulating the expression of Caspase3, Caspase9, GSK-3β, Bax, and Fyn. Findings suggest PKP and PKS are the main components of PK attenuating uranium-induced kidney damage by targeting the GSK-3β/Fyn/Nrf2 pathway, offering hope for the mitigation of uranium harmful effects on human health.