An intra-oral simultaneous bilateral inter arch isolation appliance features a generally W-shaped body having first and second cheek retractor wings, and first and second transitions respectively joining the cheek retractor wings to a tongue crib of generally U-shaped configuration with an open posterior end. In a patient worn position, each cheek retractor wing runs buccally along a respective half of a patient's dental arches to retract and isolate buccal mucosa, while the transitions curve posteriorly around the rear molars between the maxillary tuberosity and retromolar pad to carry the tongue crib inside the dental arches, where it shields and isolates the tongue. Commissure cradles at anterior ends of the cheek retractor wings hook around the patient's oral commissures at terminal ends of the appliance. Inner passageways within the body accommodate fluid extraction and/or light transmission through the appliance.