Tuberindines A and B (1 and 2), truffle alkaloids with intriguing structures, were isolated from Tuber indicum and detected in other truffle species. They appear to arise biosynthetically from amino acid and isosaccharinic units. Compound 1 upregulated the expression of organic anion transporters OAT1 and ABCG2 and significantly exhibited antihyperuricemic bioactivity in vitro and in vivo, which might support the value of truffles as a dietary supplement. © 2022 American Chemical Society.