In blood donations, chlorhexidine gluconate (CHG) and isopropyl alcohol (IPA) are routinely used for skin disinfection. Despite this measure, contamination of platelet concentrates with biofilm-forming Staphylococcus epidermidis from donor skin remains a concern in transfusion medicine. Essential oils (EOs) not only possess antibacterial abilities but have possible synergistic effects with traditional disinfectants. This study evaluated the anti-biofilm activity of EOs from four Saudi Arabian plants (Clitoria ternatea, Aerva lanata, Lavandula dentata, and Plumbago zeylanica) as potential synergistic enhancers for skin disinfection. EO composition was evaluated by gas chromatography-mass spectrometry (GC-MS), and safe EO concentrations were determined using the rabbit skin irritation test. In anti-biofilm activity assays, S. epidermidis biofilms were treated with EOs alone or in conjunction with CHG or CHG-IPA and log-reduction of bacteria was calculated. Synergistic effects were evaluated through the coefficient of drug interaction. EO concentrations up to 20% were found to be non-irritating. Most EOs exhibited some anti-biofilm activity; P. zeylanica EO exerted the strongest effect, and also displayed suggestive of synergistic action with CHG and improved CHG-IPA performance. GC-MS identified plumbagin (79%) as the main oxygenated terpenoid component in P. zeylanica EO, and plumbagin individual activity demonstrated to be almost equivalent to the activity of P. zeylanica. The effectiveness of CHG-IPA against biofilms was greatly improved by combination with P. zeylanica EO or plumbagin. These results add to the evidence that natural compounds could enhance skin disinfection agents and help lower the risk of bacterial contamination in blood products.