Stenoloma chusanum is a traditional Chinese medicinal herb with a very high total flavonoid content (TFC). The seasonal dynamics of the TFC and total phenolic content (TPC) in S. chusanum, as well as antioxidant activity, were investigated. The TFC and TPC showed clear seasonal dynamics, reaching their maxima (24.63 ± 1.34% and 9.58 ± 0.41%, respectively) in February. The TFC and TPC in the aerial parts of the plant were much higher than those in the subterranean parts; however, the antioxidant activities of the extracts from the subterranean parts were slightly higher than those from the aerial parts. Moreover, the extracts exhibited higher inhibition against tyrosinase than against arbutin (the positive control). The extract from S. chusanum collected in February was associated with the highest proliferation and apoptosis of K562 cells. The phytochemicals in the extract were analyzed using LC-MS, and were found to comprise of 12 flavonoids, five alkaloids, one sesquiterpenoid and one phenypropanoid. In conclusion, S. chusanum exhibits multiple bioactivities; these results could contribute to the therapeutic application of the plants in indigenous medicine.