Abstract: Using leaves of Xu Zishu No. 8 as the primary material, the uric acid synthesis inhibitory effect of purple sweet potato leaf water extract (PSPL) was investigated through single-factor experiments and a hyperuricemic zebrafish model. Network pharmacology approaches were subsequently employed to elucidate the major bioactive components and underlying functional mechanisms by which PSPL reduces uric acid levels. Under the optimal conditions (material-to-liquid ratio 1:10, 80 °C, 30 min), PSPL achieved a maximum XOD inhibition rate of 74.73%. Chemical profiling by HPLC-MS revealed phenolic acids, particularly chlorogenic acid and flavonoids, as the principal bioactive constituents. In a hyperuricemia zebrafish model, PSPL administration significantly reduced uric acid, ALT, AST, BUN, and creatinine levels (P<0.05). Levels of the inflammatory cytokines IL-6, TNF-α, and IL-1β were significantly reduced (P<0.05). Network pharmacology further identified 58 overlapping targets, 416 enriched GO terms, and 118 signaling pathways. Component-target-pathway mapping indicated that chlorogenic acid, caffeic acid, 6,7-dihydroxycoumarin, and isoquercitrin might interact with IL-6, TNF-α, and IL-1β, thereby regulating uric acid metabolism through pathways such as AGE–RAGE, HIF-1, and IL-17. These findings establish the biochemical basis for the hypouricemic activity of PSPL and provide a theoretical framework for the high-value utilization and advanced processing of sweet potato leaf by-products.