The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a major public health menace. Along with the conventional medicine, Ayurveda is also exploring various single herbs and compound formulations against coronavirus disease-2019 (COVID-19). The present paper is an attempt to explore the Ayurveda arsenal in strengthening the host defense system against SARS-CoV-2 infection and the relevance and necessity for whole system research. For the present study, Ayurveda classics, Ayurveda Pharmacopoeia, and Formulary were probed to obtain an insight into the diseases as well as relevant therapeutic formulations. The electronic databases Google Scholar and PubMed were searched for relevant contemporary literature. The host response to SARS-CoV-2 infection is either well-coordinated healthy or dysfunctional immune responses. It is crucial to determine the host factors that influence the consequences of host–agent interaction. Factors conducive to the maintenance of good health (Swasthyam yena anuvartate) and preventing the attacks of diseases (Ajatanam Vikaranam Anutpattikara) mentioned in Ayurveda may be considered as pivotal factors influencing homoeostatic (Samayogavahi) mechanisms of host defense system (Vyadhi-Utpada-Pratibandhakatvam and Vyadhi-Bala-Virodhitvam). Furthermore, it is observed that current research practice of Ayurveda is predominantly drug-based, reflecting the perspective of conventional medicine module, however, compromising the core principles of Ayurveda. Finding effective solutions to COVID-19 pandemic, the Ayurveda arsenal for strengthening host defense system needed to be explored. The holistic method of Ayurveda followed in its clinical practice is needed to be adopted for clinical research as well, with focus on whole system research as compared to drug-based in order to generate tangible evidence.