We report molecular interactions and inhibition of the main protease (M Pro ) of SARS‐CoV‐2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the conformational dynamics of M Pro via docking protocols and molecular dynamics simulations in all‐atom detail. We reveal the local and global dynamics of M Pro in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC 50 value of 1.39 ± 0.22 μM, which is comparable to other known inhibitors of this enzyme.