Hot water extracts of 2 groups of medicinal mushrooms have been tested from the genera Agaricus, Antrodia, Auricularia, Coprinus, Cordyceps, Hericium, Grifola, Ganoderma, Lentinus, Phellinus, and Trametes for ROS-generating activity in human cells and for DPPH-TEAC antioxidant activity. Group 1 comprised 39 commercial extracts (7 species), and group 2 comprised 12 fruiting body extracts made from 11 different species of culinary-medicinal mushrooms. For both groups, the ROS-generating activity and the antioxidant activity were strongly correlated, as were their respective polysaccharide and polyphenol contents. The extracts differ in their amounts of the latter components but not in the ratio of the two. The slopes of the correlation curves were different for both groups, which is related to the higher polyphenol content of the commercial extracts. It is suggested that possible excess cell defense-related intracellular ROS generated by mushroom extracts may be downregulated by the antioxidant components present in the same extracts.