Background: Zirconium Oxide (ZrO2) is one of the most widely used metal oxide nanoparticles with unique features that permit its usage in various medical applications, including drug delivery, targeting, labelling, and loading. Rutin is a bioflavonoid found in various natural sources and has diverse biological activities and pharmaceutical applications. Some studies have evaluated the impacts of ZrO2 NPs on aquatic creatures, but little is known about their ability to recover after exposure. Since the toxicity of ZrO2 nanoparticles is not known, it would be crucial to investigate their toxicity using zebrafish (Danio rerio) as a model organism. Objectives: In the present work, the toxicity of ZrO2 was investigated in Danio rerio using behavioural alterations, biomarkers of oxidative stress and cellular damage. The morphology of the gill tissues, as well as the optimal amount of rutin for mitigating deleterious effects was evaluated. Materials and Methods: Fish were treated for 14 days, and seven study groups were examined: control, ZrO2 exposure alone at three distinct concentrations (5 mg/L, 10 mg/L, and 20 mg/L), and combined with rutin (100 mg/L). Results: Compared to control groups, Danio rerio treated with ZrO2 alone or in combination with rutin produced worse outcomes. However, rutin-supplemented groups exhibited greater improvement than ZrO2 alone groups. ZrO2 affects cells by causing oxidative stress and decreasing the antioxidants SOD, CAT, GPx, GSH, and Vitamin C. Enhanced oxidative stress induces behavioural and morphological modifications. The structural examination of the gill tissues revealed hyperplasia, lamellar fusion, filament erosion, and a dilated marginal channel or epithelial lifting. Conclusion: According to our data, the sub-lethal concentration of ZrO2 NPs for Danio rerio is 10 mg/L. Although ZrO2 was detrimental to the groups exposed to it, supplementing 100 mg/L of rutin was able to protect against its toxicity.