Background: Kidneys as vital organs remove waste material from blood. Additionally, they may also have a role in the electrolyte balance, regulation of blood pressure, and red blood cell genesis. Kidney diseases may be caused by several factors such as ischemia/reperfusion injury, diabetes, and nephrotoxic agents. Oxidative stress and inflammation are involved in the pathogenesis and progression of kidney diseases. Traditionally, natural antioxidants are used for treatment of renal failure in various countries. Summary: People usually select natural antioxidants since they have an opinion that herbal medicine has not any important side effects. Nigella sativa is a flavoring herb that is widely used as a condiment and as a remedy for many disorders. Thymoquinone (TQ), the most important component of black seeds, mainly oil, is considered as an active agent responsible for a lot of the seed’s useful effects. This review describes the protective roles and related mechanisms of TQ against renal disorders. The search terms, including TQ, antioxidant, renal ischemia-reperfusion, diabetic nephropathy, and nephrotoxic agent were searched in scientific databases. TQ showed anti-inflammatory and antioxidant properties in animal and in vitro models of several renal diseases caused by inflammation and oxidative stress. Key Messages: Experimental studies have shown beneficial effects of TQ against renal diseases; however, well-designed clinical trials in humans are required to confirm these effects.