Abstract: Cocrystallization is emerging as a promising method to enhance the water solubility of drugs. Puerarin (PUE) and quercetin (QUE) possess valuable pharmaceutical properties like antioxidant and antitumor effects but suffer from poor water solubility. To address this issue, we prepared cocrystals of puerarin-4,4’-bipyridine (PUE-4,4’-BIP) and quercetin-2,4’-bipyridine (QUE-2,4’-BIP). In artificial gastric fluid, the solubility and dissolution rates of both puerarin and quercetin significantly increased after cocrystal formation. Furthermore, toxicity analysis via LD50 testing revealed lower toxicity for PUE-4,4’-BIP and QUE-2,4’-BIP cocrystals.