Flavonoid compounds are widely present in fruits, vegetables, and cereals. Given their role in defense systems, they are significant for both plants and people. They protect plants from biotic and abiotic challenges, as well as treat or prevent oxidative stress-related disorders in humans. They are utilized in the pharmaceutical sector, as functional foods, and as nutraceuticals for these reasons. Zebrafish are regarded as one of the most adaptable experimental animals. They are an excellent model for drug testing because of their transparent embryos, tiny size, quick development, and resemblance to higher vertebrates. Its use enables a thorough evaluation of new targets and is closely related to the assessment of the bioactivity, toxicity, and side effects of novel drug candidates that are off-target. As a result, it may be an appropriate model for drug screening and the optimization of novel candidates. The most significant studies on zebrafish as a useful experimental model for researching diseases linked to oxidative stress are summarized in this article with a focus on the biological effects of flavonoids. © 2025 Elsevier B.V., All rights reserved.