Euphorbia greenwayi P.R.O. Bally & S. Carter, is a member of the Euphorbiaceae family, which includes numerous species used in folk medicine to cure a variety of diseases. However, there have been few reports regarding this species. E. greenwayi aerial parts' analysis was done using UPLC-MS/MS technique for methanol extract (ME). The negative ion mode resulted in the identification of three phenolic acids; chlorogenic, ferloyl malic acids, and brevifolin carboxylic acid hexoside. Four flavonoids; rutin, astragalin, kaempferol-O-acetyl-hexoside, and isorhamnetin-O-rutinoside. Additionally, eight diterpenes were identified as ingenol mebutate, deoxy-oxoingenol butanoate, and ingenol dibenzoate with its isomer, besides, phorbol acetate, phorbol diacetate and its isomer, and phorbol. Also, five triterpenes; taraxasterol, lupeol, β-Sitosterol, hydroxytaraxasterol, and hydroxyoleanolic acid were detected by the positive ion mode. ME was fractionated using chloroform (CF) and ethyl acetate (EF) to evaluate phenolic and flavonoid contents, antioxidant, and anti-inflammatory potential. EF had the greatest flavonoid and phenolic content 141±9 μg RE/mg & 108.76±3 μg GAE/mg, respectively. EF exhibited the highest antioxidant activity in DPPH, metal chelation, and ORAC assays: 30.14±1 μg/mL, 7.36±0.4 μmole EDTA eq/mg, and 7118.83±4 µmole Trolox eq/mg respectively. ME revealed the highest anti-inflammatory activity against the expression of TNF-α and IL6 cytokines 0.241±0.01 and 0.321±0.02 fold change respectively.