Hyperuricemia (HUA) is a metabolic disease characterized by high levels of uric acid (UA) in the blood and varying degrees of kidney damage. Desirable nanoliposomes should simultaneously exhibit efficient biocompatibility and effective drug delivery. However, they both usually require special structural properties. Herein, we propose a strategy to prepare nanoliposomes with varying rigidity by replacing cholesterol (CH) with phytosterol esters (PE). The results showed that the particle size of PE naringenin nanoliposomes (PE-NAR) was 179.5 nm, and the encapsulation efficiency (EE) was 79.93%. In atomic force microscopy (AFM) tests, PE-NAR showed a 1-fold increase in rigidity compared to CH naringenin nanoliposomes (CH-NAR). By observing the effects of naringenin nanoliposomes (NAR-NLs) on the physiological and biochemical indicators in HUA mice, we explore its impact on kidney damage and inflammatory pathways in HUA mice. The results show that NAR-NLs significantly inhibit UA levels and improve kidney damage. Compared to oral naringenin, NAR-NLs generally enhance the in vivo antioxidant effects of naringenin. Furthermore, high-rigidity PE-NAR downregulated the renal inflammatory factor interleukin-1β (IL-1β) to 6.67%, demonstrating the highest inhibitory effect. Further experiments have demonstrated that naringenin exerts a protective effect in kidney injury by inhibiting the activation of NOD-like receptor protein 3 (NLRP3) inflammasome and reducing oxidative stress within the body. In summary, by adjusting the rigidity of the nanoliposomes, the oral administration of naringenin can effectively improve the alleviation of HUA.