Wedelolactone (WDL) is a couma ether compound extracted from the traditional Chinese medicinal plant, Eclipta prostrata. It is a natural polyphenol that exhibits a variety of pharmacological activities, such as anti-inflammatory, anti-free radical scavenging, and antioxidant activities in the bone, brain, and ovary. However, its effect on embryonic development remains unknown. The present study explored the influence of WDL supplementation on porcine oocytes culture in vitro, its underlying mechanisms, and the levels of Kelch-like ECH-associated protein 1/nuclear factor-erythroid 2-related factor 2/antioxidant response element. The results showed that WDL (2.5 nM) significantly increased the blastocyst formation rate, mitochondrial activity, and proliferation ability, while reducing the reactive oxygen species accumulation, apoptosis, and autophagy.