This study aimed to investigate the biological activities, including polyphenolic content, flavonoid content, and antioxidant activities, of various cultivars of Korean perilla leaves. The results indicated that among nine cultivars (Namcheon dlggae, Saedora, Nulbora, Donggel 1, Donggell 2, Soim, Sangyeop, Somirang, and Saebom) of perilla leaves, the total polyphenolic content (gallic acid equivalent mg/g, GAE) was the highest in “Nulbora,” while it was lowest in Namcheon dlggae. Moreover, flavonoid content in the extracts of nine cultivars leaves was in the range of 132.93~268.50 mg catechin equivalent/g sample. The antioxidant effects of the perilla leaves were determined using two different in vitro bioassays measuring DPPH and ABTS radical-scavenging activities. The results revealed that antioxidant activity was also higher in “Nulbora” compared with other cultivars. Xanthin-oxidase-inhibition activity ranged from 65.65% to 80.58%, with “Nulbora” exhibiting the highest activity, although the difference with other cultivars was not significant. “Nulbora” extracts reduced the expression of pro-inflammatory genes and several cytokines, including IL-6 activation induced by LPS in macrophages in the range of 100–50 μg/mL. These results suggest that extracts from perilla leaves can be used as bioactive and functional materials that could be important in industrial applications in the future.