Background: Crataegus meyeri A. Pojark is one of Iran›s most well-known medicinal plants. This study aimed to assess the cytotoxic, antioxidant, and anti-inflammatory properties of the methanolic extract of Crataegus meyeri (MCM) leaves.Methods: MCM was prepared from dried leaves. First, the cytotoxic impact of MCM was determined via the MTT test. Then, the anti-inflammatory activity of MCM on the lipopolysaccharide (LPS)-exposed J774A.1 cells was examined by measuring NO production and cyclooxygenase-2 (COX-2) gene expression using the Griess test and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. MCM antioxidant activity was assessed using the FRAP and DPPH tests.Results: MCM was shown to be non-cytotoxic against J774A.1 cells at≤125 and≤62 μg/mL concentrations after 24 and 48 hours, respectively. It also significantly attenuated NO generation in LPS-treated J774A.1 cells at 62 and 125 μg/mL after 24 hours and 62 μg/mL after 48 hours. The extract significantly reduced COX-2 gene expression at concentrations of 62 and 125 μg/mL after 24 hours and at concentrations of 15, 31, and 62 μg/mL after 48 hours. Moreover, the results indicated that MCM at all concentrations exhibited lower antioxidant activity than vitamin C, but the difference was insignificant. Furthermore, MCM could reduce the viability of most of the studied cancer cell lines at concentrations of 250 and 500 μg/mL.Conclusion: The findings of the present study suggest that MCM may show therapeutic potential for the treatment of inflammatory diseases, a finding that requires clinical trials.