COVID-19, a pandemic disease has affected 480 million people and caused 6 million deaths around the world. Despite the progress made in COVID-19 drug discovery, SARS-CoV-2, the causative agent of this disease continuously mutates and rapidly evolves into new variants. This increases the challenges in drug discovery for COVID-19. As natural products serve as sources of drugs forever, this study applies computational techniques in predicting the natural compounds in herbs and spices of household origin as SARS-CoV-2 spike and protease inhibitors and also verifies the top hits against spike and protease mutants associated with SARS-CoV-2 variants of concern. This study reveals Hesperidin, Diosgenin, Fenugreekine, Epigallocatechin gallate and Quercetin as SARS-CoV-2 spike and protease inhibitors, which acts better than the drug Remdesivir. The efficiency of the top hits was also been verified against the mutants, which reveals Diosgenin and Fenugreekine as the most efficient natural compounds against SARS-CoV-2 spike mutants (N501Y, E484K, K417N and K417T), which are associated with SARS-CoV-2 variants of concern. Additionally, Hesperidin is proven to have better binding efficiency against Mpro mutants (Y54C, A191V, T190I and N142S). Overall, this study concludes that Hesperidin, Diosgenin and Fenugreekine could combat both SARS-CoV-2 and its variants effectively. © 2024 Elsevier B.V., All rights reserved.