Acute kidney injury (AKI) has been increasingly reported in critically-ill COVID-19 patients. Moreover, there was significant positive correlation between COVID-19 deaths and renal disorders in hospitalized COVID-19 patients with underlying comorbidities who required renal replacement therapy. It has suggested that death in COVID-19 patients with AKI is 3-fold higher than in COVID-19 patients without AKI. The pathophysiology of COVID-19-associated AKI could be attributed to unspecific mechanisms, as well as COVID-19-specific mechanisms such as direct cellular injury, an imbalanced renin-angiotensin-aldosterone system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. To date, there is no specific treatment for COVID-19 and its associated AKI. Luteolin is a natural compound with multiple pharmacological activities, including anticoronavirus, as well as renoprotective activities against kidney injury induced by sepsis, renal ischemia and diverse nephrotoxic agents. Therefore, in this review, we mechanistically discuss the anti-SARS-CoV-2 and renoprotective activities of luteolin, which highlight its therapeutic potential in COVID-19-AKI patients.