The SARS-CoV-2 coronavirus is causing the COVID-19 pandemic, which has engulfed the world threatening millions of human lives. In order to enter human body, the SARS-CoV-2 virus uses its spike protein to bind to the human angiotensin-converting enzyme 2 (ACE2) protein, which allows the entry of the virus. Thus, the interaction between the receptor-binding domain of the spike glycoprotein (S protein) of SARS-CoV-2 and the peptidase domain of ACE2 is the key for virus infection. Compounds that bind to ACE2 and prevent virus S protein interaction will be useful to prevent and treat COVID-19. Using our unique on-bead two-color combinatorial cell-screening technology (OBTC), we discovered two new peptoid (oligo-N-substituted glycine) compounds (ACE2P1, ACE2P2) that specifically bind to the ACE2 protein. We have shown that both peptoids ACE2P1 and ACE2P2 bind to ACE2 expressing cells, but not the cells that do not have ACE2. More importantly, both ACE2P1 and ACE2P2 can block the binding of SARS-CoV-2 spike protein binding to the ACE2 protein in the in vitro pull down assay. The data suggests that both compounds can potentially block the entry of SARS-CoV-2 into human cells. Furthermore, ACE2 is an important enzyme that maintains normal blood pressure. Our data indicates that ACE2P1 and ACE2P2 do not inhibit this ACE2 enzyme activity, suggesting that these compounds will not have side effects affecting the maintenance of the blood pressure. We will test whether ACE2P1 and ACE2P2 can prevent the entry of pseudo and real SARS-CoV-2 virus into human cells near future. Also, we are designing multimeric versions of these peptoids to develop more potent derivatives. Our plan is to develop these compounds as nasal sprays and/or eye drops that can prevent COVID-19 as well as injection/oral dosage forms for COVID-19 treatment. Peptoids closely resembles peptides and are protease-resistant, highly tissue permeable, and non-immunogenic. Peptoids are high stable at room temperature and the development (synthesis, optimization) is very economical, presenting high drug-like properties.