As a continuation of our research on the pesticide development of Polygonum orientale L., the chemical constituents of the seeds of P. orientale were systematically investigated. Eleven natural compounds (PO-1 to PO-11) were isolated from the EtOAc extract of P. orientale. Notably, compound PO-9 and its dimeric compound PO-10 were first isolated from P. orientale and possessed excellent acaricidal activity against Tetranychus cinnabarinus. With PO-9 and PO-10 as the lead compounds, two series of cinnamate derivatives were further synthesized, and their acaricidal, insecticidal, and fungicidal activities were evaluated systematically. The insecticidal activity results showed that dimeric derivative NKY-70 displayed the highest acaricidal activity against T. cinnabarinus and insecticidal activities against Brevicoryne brassicae and Myzus persicae. Furthermore, most of these compounds showed excellent in vitro antifungal activity against plant fungi. Compound NKY-66 displayed the highest and broad spectrum of antifungal activity against 23 fungi, and the respective EC50 values were 0.09, 0.08, 0.12, 0.18, 0.12, and 0.09 mg/mL against Valsa mali, Fusarium oxysporum f. sp. cucumerinum, Fusarium graminearum, Magnaporthe oryzae, Colletotrichum capsici, and Phytophthora infestans, which were more potent than those of chlorothalonil and procymidone. Moreover, the in vivo fungicidal evaluation also demonstrated that compound NKY-66 could effectively control plant fungal diseases in the greenhouse and in the field, such as damping off, powdery mildew, and cucumber downy mildew. Therefore, these findings implied that the cinnamate derivative NKY-66 displayed superior in vitro and in vivo fungicidal activities and could be a potential candidate against plant fungal diseases.