Since the outbreak of COVID-19, the pandemic caused by SARS-CoV-2 infection is still spreading at an alarming rate and has caused huge loss of life and economic damage worldwide. Although more than one year has passed, effective treatments for COVID-19 and other pathogenic coronaviruses have not yet been developed. Therefore, the development of SARS-CoV-2 inhibitors is an urgent priority. Given that the M<sup>pro</sup> sequences of SARS-CoV-2 and SARS-CoV-1 are 100% identical in the catalytic domain for protein cleavage, the viral main protease (M<sup>pro</sup>) is one of the most extensive drug targets in all the drug targets being investigated for SARS-CoV-2. To provide scientific researchers with timely anti-SARS-CoV drug development information for M<sup>pro</sup>, we focus on the past and current drug design and development strategies for M<sup>Pro</sup> in this review. We believe that this review will provide meaningful guidance for the design and development of innovative drugs against COVID-19 and other pathogenic coronaviruses in the future.