1. Flavonoids are a group of polyphenolic plant metabolites most commonly known for their antioxidant activities. They also show inhibitory activities on molybdo-flavoenzymes family of enzymes which are involved in biotransformation of some exogenous and endogenous chemicals. Most notably, aldehyde oxidase (AO), a member of this family, is responsible for metabolism of some therapeutic agents. On the other hand, there are some therapeutics which inhibit AO. As flavonoids are ubiquitous in human diet and have potential to interact with AO, it is important to investigate their effects at the molecular details. 2. The inhibitory effects of 15 flavonoids on the activity of rat liver AO were assessed. Quantitative structure-activity relationship studies were performed using genetic algorithm coupled partial least square and stepwise multiple linear regression methods to elucidate the important structural properties responsible for the observed inhibitory effects. To further understand the mode of interaction between these flavonoids and AO, a homology model of the enzyme was built and flavonoids were docked into its active site. The most important amino acids involved in the interactions were identified. 3. Quercetin, myricetin and genistein were the most potent inhibitors establishing favorable interactions with the enzyme. However, the glycosylated flavonoids showed relatively weaker inhibition which may be attributed to their hindered binding into the active site of AO by bulky sugar groups.