Accumulating evidence shows that oxidative stress and inflammation contribute to the development of cardiovascular disease. It has been suggested that propolis possesses antioxidant and anti-inflammatory activities. In this study, the antioxidant and anti-inflammatory effects of the main flavonoids of propolis (chrysin, pinocembrin, galangin, and pinobanksin) and propolis extract were researched. The results showed that the cellular ROS (Reactive oxygen species) levels, antioxidant enzymes, Nrf2 (Nuclear factor erythroid 2-related factor 2) nuclear translocation, and the expression of NQO1 (NAD(P)H:quinone oxidoreductase 1) and HO-1 (heme oxygenase 1) were regulated by different concentrations of individual flavonoids and propolis extract, which showed good antioxidant and pro-oxidant effects. For example, ROS levels were decreased; SOD and CAT activities were increased; and the expression of HO-1 protein was increased by chrysin. The results demonstrated that NO (Nitric Oxide), NOS (Nitric Oxide Synthase), and the activation of the NF-κB signaling pathway were inhibited in a dose-dependent manner by different concentrations of individual flavonoids and propolis extract. Moreover, the results revealed that the phytochemicals presented antioxidant effects at lower concentrations but pro-oxidant effects and stronger anti-inflammatory effects at higher concentrations. To maintain the balance of antioxidant and anti-inflammatory effects, it is possible that phytochemicals activate the Nrf2 pathway and inhibited the NF-κB (Nuclear factor kappa B) pathway.