Uric acid (UA) is an important endogenous antioxidant, but its insolubility in serum poses a risk of hyperuricemia. We hypothesized that a tautomeric isomer of UA is equivalent to hydroquinone or p-aminophenol, which can be oxidized to quinone/quinoimine and thus act as a radical scavenger. Based on this hypothesis, a series of UA analogs were designed and synthesized. In the DPPH radical scavenging assay, active compounds were found to be hydroquinone or p-aminophenol equivalents, and a highly functionalized UA structure was not essential for radical scavenging activity. Potent 5-hydroxyindolinones (1a, 2a, and 3a) exhibited sufficient radical scavenging activity, along with high solubility and low cytotoxicity. Further analysis revealed that the common structure of active compounds was hydroxybenzimidazoline or hydroxyindoline, and the moieties required for the antioxidant activity of UA were 2-CO and 7-NH or 9-NH (as analogs 5 and 6 showed greater antioxidant activity than UA). The most active analog, 2a, had 150 times higher activity than UA. Notably, the pyrimidine-trione moiety of UA was not essential, while the hydroquinone/p-aminophenol-equivalent structure was effective for antioxidant activity. Among the synthetic analogs, 1a, 2a, and 3a demonstrated remarkable radical scavenging activity, low cytotoxicity, and improved solubility in neutral buffer compared to UA, making them potential candidates for novel potent antioxidants.