A series of novel ligustrazinylated derivatives was designed, synthesized and evaluated for their protective effects against hydrogen peroxide (H2O2)-induced oxidative damage on ECV-304 cells, and also assayed for their inhibition effects on platelet aggregation induced by adenosine diphosphate (ADP). Biological results showed that some compounds exhibited moderate to potent activities in one or both of the assays. Among these compounds, compound 3 displayed the highest protective effect on the damaged ECV-304 cells with EC50 ¼ 0.0040 mM, and compound 1c was the most active platelet aggregation inhibitor (EC50 ¼ 0.40 mM). Structure–activity relationships were briefly discussed.