Plasma-activated water (PAW) treatment is an effective technique for the quality retention of fresh vegetables with cold atmospheric plasma using controllable parameters. This study investigated the effect of PAW on the postharvest quality of shepherd’s purse (Capsella bursa-pastoris). The results displayed that PAW treatment with an activation time of 5, 10, 15, and 20 min reduced the yellowing rate and weight loss of the shepherd’s purse during 9 days of storage. Compared with untreated samples, PAW treatment at different times reduced the number of total bacteria, coliform, yeast, and mold by 0.18–0.94, 0.59–0.97, 0.90–1.18, and 1.03–1.17 Log CFU/g after 9 days of storage, respectively. Additionally, the treatments with PAW-5 and PAW-10 better preserved ascorbic acid, chlorophyll, total phenol, and total flavonoid contents. They also maintained the higher antioxidant and CAT activity and inhibited the formation of terpenes, alcohols, and nitrogen oxide compounds of the shepherd’s purse at the end of storage. The microstructural result illustrated that the cells of the shepherd’s purse treated with PAW-5 and PAW-10 were relatively intact, with a small intercellular space after storage. This study demonstrated that PAW treatment effectively improved the postharvest quality of shepherd’s purse.