Nowadays, infectious diseases are subsequently increasing with the ongoing pandemic and thus there is a basic need for treatment. As medicines are quite expensive and not easily available. Thus, scientists are exploring new ways to develop inexpensive and resistant drugs. As we know plants extract are a rich source of secondary metabolites and consist of very valuable chemical properties. Considering all these facts in mind the present work for at first phytochemical screening by GC–MS of the active components of fractionated extractions, ethyl acetate, hexane, and methanol plant extracts of Euphorbia inarticulate Schweinf collected from the Jazan region were investigated, followed by a screening of its antioxidant and antimicrobial activity. The antioxidant activity of the methanolic extract revealed high inhibitory activity with the IC50 value of ascorbic acid, and the methanolic extract was found to be 36.67μg/mL, and 52.94μg/mL respectively. The antimicrobial activities of these extracts were examined on microorganisms such follows: Streptococcus pneumoniae and Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus fumigants by the agar diffusion method. Methanol extract showed against B. subtilis and S. pneumoniae (Gram-positive bacteria) MIC values of 1.95 and 0.98µg/mL, respectively as that recorded for the standard Ampicillin. While against Pseudomonas aeruginosa and E. coli (Gram-negative bacteria) MIC values were 1.95 and 0.98µg/mL, respectively. Moreover, MIC values recorded for the standard were 1.95 and 0.49µg/mL, respectively. The MIC value recorded for methanol extract against A. fumigatus only (Fungi) was 1.95μg/mL, and that for the standard Amphotericin B were 0.98 and 0.49μg/mL respectively.