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The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from <i>Magnoliae officinalis</i> Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3<i>H</i>)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, <b>6a</b> and <b>6p</b> demonstrated antiviral entry effect with IC₅₀ values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC₅₀ value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that <b>6p</b> binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of <b>6p</b> on SARS-CoV-2 spike RBD’s binding with ACE2. Importantly, <b>6a</b> and <b>6p</b> (TC₅₀ > 100 μM) also had higher biological safety for host cells than honokiol (TC₅₀ of 48.23 μM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although <b>6p</b>’s antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.