The changes of bioactive substances in peels and sarcocarps of three different varieties of Kadsura coccinea (Dahong, Fenhong, and Zihei) were evaluated by an in vitro simulation model. In this study, three varieties of K. coccinea fruits were digested in vitro to compare the changes and differences in antioxidant activity (DPPH, ABTS, FRAP) and bioaccessibility. The results showed that before digestion the highest content of total phenolics (TPC) (2.265 ± 0.127 mg GAE/g DW) and the highest content of flavonoids contents (TFC) (10.379 ± 0.093 mg GAE/g DW) were found in Fenhong fruit. The highest release of TPC and TFC after simulated gastric digestion was observed in the Dahong and Zihei sarcocarp, which increased by 98.7 and 20%, respectively. During oral and intestinal digestion, the content of bioactive compounds showed a decreasing trend. The radical scavenging ability of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), [2,2-azino-bis(3-ethylbenzothiazoline) (ABTS)] sulfonic acid free radical scavenging ability, and ferric ion reducing antioxidant power (FRAP) results showed that the antioxidant capacity of K. coccinea fruits increased most significantly (26.9∼181%) in gastric digestion stage and then decreased after intestinal digestion stage. The recoveries of TPC and TFC were all increased after whole simulated digestion, as well as their bioaccessibility in sarcocarps was higher than those in peels, especially for the bioaccessibility of TPC and TFC in Dahong reached 50.53 and 48.19%, respectively. These results indicated that the peel and sarcocarp of K. coccinea had good antioxidant activity, with high bioaccessibility of phenolics could be a promising antioxidant source for the food industry.