This chapter has exclusively provided the overview of a novel application of chitosan derivatives and nanoparticles to combat COVID-19. A disease that sent shockwaves globally with its devastating impact and unprecedented ability to disrupt all aspects of life, leaving the world in awe and bewilderment for an extended period. The chapter has provided a detailed taxonomy and background of the disease COVID-19 and the virus SARS-CoV-2 responsible for the outbreak in 2019. It was however emerged that the introduction of each of the viruses into humans was likely facilitated by independent unknown external factors. The taxonomy has been given in detail. The immunology and immunopathology of COVID-19 has also been described in detail. Coronaviruses are enveloped viruses with a positive-sense RNA-strand genome of ~ 30,000 bases. The first line defense against COVID-19 infection is a quick and harmonized innate immune response; however, unregulated and uncontrolled immune responses can cause immunopathology. The innate immune system uses various pattern recognition receptors (PRRs) to detect the presence of viruses. The chapter has also provided the details of adaptive immunity to SARS-CoV-2 which deals with the protection from viral infection and disease. The chapter has also discussed the common antiviral approaches and limitations. The role and applications of chitosan in this connection have been elaborated. Direct antiviral effects and immune-boosting effects of chitosan have also been highlighted. Chitosan has been proven as a good drug delivery vehicle for the treatment of viral infections. Chitosan bearing such pharmacological properties makes it widely studied compound thus revealing that chitosan affects the immune system of biological system and can improve the defense mechanism against foreign viruses effectively.