Microcystin-leucine arginine (MC-LR), the most prevalent and dangerous microcystin, poses high risks to living organisms, especially fish and mammals. Although many studies have focused on the toxic effect on fish and mammals exposed to MC-LR, works that incorporate published data into a comprehensive comparison and analysis are still limited. Here, the adverse effects of oxidative stress markers, health, functional traits, and performance traits in fish and mammals were systematically verified by collecting data from 67 studies for the first time. Notably, we first found that the activities of malondialdehyde (MDA) (p < 0.05) and lactoperoxidase (LPO) always showed increases, whereas the growth (performance traits) always had a significant decrease (p < 0.001) under all variables of MC-LR exposure, i.e., exposure time, exposure concentration, exposure route, and even life stage. Additionally, our study first verified that the activities of MDA and LPO can be employed as oxidative stress indicators of MC-LR effects in fish and mammals instead of other biomarkers of oxidative stress, such as superoxide dismutase (SOD) and catalase (CAT), considered by previous studies. Growth may be regarded as a highly sensitive indicator of MC-LR toxicity in mammals and fish. At the same time, we first found that the impact of MC-LR exposure concentration on LPO, MDA, and growth is higher than that of exposure time, exposure route, and different life stages using the random forest (RF) model. In short, this work sheds light on the potential biochemical and individual toxicity of MC-LR exposure in fish and mammals.