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With the ever-increasing antibiotic resistance in the medical field, there is a need now more than ever to develop natural antibacterial alternatives. In order to address this growing concern, the natural compound Curcumin and Carvacrol were investigated against Escherichia coli (E. coli), Bacillus subtilis (B. subtilis), Staphylococcus epidermidis (S. epidermidis), and Pseudomonas aeruginosa (P. aeruginosa). Curcumin, which is an active ingredient in the well-known Turmeric plant, has been shown to have antioxidant, anti-inflammatory, and anti-microbial properties. Carvacrol, which is found in Oregano and other essential oils, has shown antimicrobial properties on a wide range of bacterial species. E. coli is a Gram-negative rod-shaped bacterium that is known to cause many bacterial infections that include urinary tract infection (UTI), cholecystitis, bacteremia, cholangitis, and other clinical infections such as pneumonia as well. B. subtilis, which is a Gram-positive bacterium, can also cause infections such as bacteremia and pneumonia but also endocarditis and septicemia. Gram-negative P. aeruginosa can cause diseases such as respiratory tract infections, UTIs, and gastrointestinal infections. Gram-positive S. epidermidis is a bacterium that can cause diseases such as endocarditis and dermatitis. The aim of this study is to investigate the antimicrobial activity of curcumin and carvacrol against these bacteria species using microplate assay and colony-forming unit (CFU) assays. The growth monitoring results indicated that 100 µg/mL of curcumin and 0.1% of carvacrol significantly inhibited four bacterial species. The cell number data obtained from the fluorescent microscopy indicated that curcumin could reach 3.26, 1.75, 3.17, and 1.65 log reduction in S. epidermidis, P. aeruginosa, E. coli, and B. subtilis, respectively. Furthermore, synergistic bacterial effect of curcumin and carvacrol with antibiotics with differing modes of action were assessed. The disc-diffusion assay results suggested no significant antibacterial synergism was observed for either curcumin or carvacrol with the selected four antibiotics.