Quercetin (Qct) is a flavonoid that belongs to the group of the most bioactive polyphenolic compounds. It is abundantly found in our diet, and it has many beneficial effects on human health because of its potent antioxidant properties. Qct has shown cardioprotective effects against doxorubicin, cyclophosphamide, daunorubicin, and lindane and nephroprotective effects against methotrexate, doxorubicin, gentamicin, valproic acid, cadmium, potassium dichromate, fluoride, mercury chloride, 2,3,7,8-tetrachlorodibenzo-p-dioxin, titanium dioxide nanoparticles, and gold nanoparticles. In the current review, we discussed the molecular and biochemical mechanisms involved in the cardio- and nephroprotective effects of Qct. The main purpose of this review was to identify the cardio- and the nephroprotective mechanisms of Qct against several drugs and chemicals to encourage further studies to investigate the potential protective effect of Qct.