Seaweeds are valuable sources of bioactive compounds in biomedicine, cosmetics, food, and pharmacology. The purpose of this investigation was to study the antimicrobial properties of organic solvent extracts from two red seaweed species (Melanothamnus somalensis & Gelidium omanense), and two brown seaweed species (Jolyna furcata & Nizamuddinia zanardinii) compiled from the southern coastline of Oman against several bacterial strains of global health concern (Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa) and one fungal strain (Candida albicans). Five organic solvents were used sequentially to achieve extraction. The solvents were applied in the following order: hexane, dichloromethane, ethyl acetate, acetone, and methanol. Only the methanol extract of Nizamuddinia zanardinii (MeNZ) showed interesting antimicrobial activity; the inhibition zone was 13 ± 1 mm. Furthermore, MeNZ was fractionated, and fraction 1 (MeNZ-F1) was recognized to have antimicrobial activity; the inhibition zone was 14.66 ± 0.57 mm. The stock concentration exhibited higher antimicrobial activity compared to the diluted concentrations after 3 h of incubation. The TEM and SEM results indicated that E. coli treated with the active fraction exhibited irregular shape, rough surface, and leakage of cellular content. Additionally, ribosomes were clustered and directed toward the inner membrane of the bacteria, while the DNA clustered in the center of the cell. In conclusion, the methanol extract of Nizamuddinia zanardinii has shown high efficacy against pathogenic bacteria and fungi. Therefore, it can be a valuable candidate for improving/developing antimicrobial drugs in the pharmaceutical and food industries.