SARS-CoV-2 M (Mpro) is the critical cysteine protease in coronavirus viral replication. Tea polyphenols are effective M inhibitors. Therefore, we aim to isolate and synthesize more novel tea polyphenols from Zhenghedabai (ZHDB) white tea methanol-water (MW) extracts that might inhibit COVID-19. Through molecular networking, 33 compounds were identified and divided into 5 clusters. Further, natural products molecular network (MN) analysis showed that MN1 has new phenylpropanoid-substituted ester-catechin (PSEC), and MN5 has the important basic compound type hydroxycinnamoylcatechins (HCCs). Thus, a new PSEC (1, PSEC636) was isolated, which can be further detected in 14 green tea samples. A series of HCCs were synthesized (2–6), including three new acetylated HCCs (3–5). Then we used surface plasmon resonance (SPR) to analyze the equilibrium dissociation constants (K) for the interaction of 12 catechins and M. The K values of PSEC636 (1), EGC-C (2), and EC-CDA (3) were 2.25, 2.81, and 2.44 μM, respectively. Moreover, compounds 1, 2, and 3 showed the potential M inhibition with IC 5.95 ± 0.17, 9.09 ± 0.22, and 23.10 ± 0.69 μM, respectively. Further, we used induced fit docking (IFD), binding pose metadynamics (BPMD), and molecular dynamics (MD) to explore the stable binding pose of M-1, showing that 1 could tightly bond with the amino acid residues THR, HIS, CYS, TYR, GLU, and ASP. The computer modeling studies reveal that the ester, acetyl, and pyrogallol groups could improve inhibitory activity. Our research suggests that these catechins are effective M inhibitors, and might be developed as therapeutics against COVID-19.