Limonium socotranum and Peperomia blanda are used in ethnomedicine to treat several diseases, such as infection, cancer, and inflammation. P. blanda (family: Piperaceae) is from the genus Peperomia, and mostly found in Madagascar, Yemen, USA to South America, while L. socotranum (family: Plumbaginaceae) from the genus Limonium and this species is found only on Socotra Island, Yemen. These plants have attracted great interest in recent years because of their phytochemical contents. Consequently, the current study is aimed to investigate the phytochemical constituents, the cytotoxic and antimicrobial activities of L. socotranum (leaves and stem) and P. blanda extracts. Successive extraction had been performed which resulted in nine crude extracts. Phytochemical screening of the extracts was then conducted using qualitative chemical analysis. The antimicrobial activity of the plant extracts was determined using the well diffusion method against eleven selected pathogenic microbes and the minimum inhibitory concentrations (MIC) were measured. The cytotoxic activities of the plant extracts against MCF-7 and HepG2 cell lines were investigated using sulforhodamine B assay. It was noted that methanol leaves extract from L. socotranum exhibited higher antibacterial activity against Micrococcus luteus (MIC 15.6 μg/mL), Staphylococcus aureus (MIC 125 μg/mL) and Pseudomonas aeruginosa (MIC 125 μg/mL), than stem parts, while petroleum ether extract displayed stronger antifungal activity, with MIC of 125 μg/mL. On the other hand, petroleum ether extract of P. blanda was effective against Gram-positive bacteria and exhibited moderate antifungal activity. Petroleum ether extract of P. blanda displayed cytotoxic activity against MCF-7 cells, with an IC50 of 4.60 ± 0.02 μg/mL, while the methanol extracts showed higher activity against the HepG2 cell line, with an IC50 of 13.90 ± 0.14 μg/mL. Phytochemical findings confirmed the presence of flavonoids, alkaloids and terpenoids. The promising obtained results suggest the potential use of these plants in cancer and antimicrobial therapies.