The outbreak of new coronavirus disease-20119 or COVID-19 infection has become a global health emergency at the beginning of this year. Currently, no specific vaccines and therapeutic medications are available to treat this disease. Even though several vaccine candidates are under investigation, it will take some time to make them available for the mass population. Hyperinflammation due to excessive cytokine release in COVID-19 infected patients with other inflammatory diseases makes lethal effects, including multiorgan failure and even death. The increasing gain of insight about the pathophysiology of this novel coronavirus enables experts to consider some commonly available anti-inflammatory drugs as potential immunomodulatory candidates for the cytokine release syndrome (CRS) treatment in COVID-19 infection. This review was conducted to discuss all the possible signalling pathways involved in COVID-19 related hyperinflammation. It also emphasized on the efficacy of both synthetic and natural therapeutic drugs for immunomodulation in the COVID-19 related CRS treatment.