Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by ¹H NMR, ¹³C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC₅₀ = 0.26 μmol·L^-1) was 6.7 times than the lead compound A (IC₅₀ = 1.73 μmol·L^-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.