The SARS-CoV-2 virus has spread worldwide, affecting millions, and showing no signs of slowing down or stopping. Secondary metabolites have been important sources of medicine for millennia. In this study, the secondary metabolites of Psidium guajava L. and Piper nigrum L. were screened for binding to three key coronavirus disease (COVID-19) associated proteins, namely, the viral spike protein, its target ACE2, and its primer TMPRSS2. Through molecular docking, the compounds isoquercetin, terpinyl acetate, morin-3-O-lyxoside, guineensine and brachyamide A were found to have considerable binding to these three receptors. With almost benign ADME-Tox profiles and energetically favorable binding, the secondary metabolite compounds caryophyllene, terpinyl acetate, morin and morin glycosides may be considered for assays, further development, and clinical investigations.