Dental caries, the breakdown of tooth enamel by bacteria infection that causes cavities in the enamel, is the most common chronic disease in individuals 6–19 years of age in the U.S. Optical detection of caries has been shown to be sensitive to the presence of bacteria and the resulting demineralization of enamel. The scanning fiber endoscope (SFE) is a miniature camera system that can detect early stages of caries by performing high-quality imaging and laser fluorescence spectroscopy with 405 nm excitation. Because optical imaging of caries does not involve radiation risk, repeated imaging of the teeth is acceptable during treatment of the bacterial infection to monitor healing. A disposable handpiece was designed and fabricated to position the flexible fiber optic SFE probe for quantitative measurements. Plastic 3D-printed handpiece prototypes were tested with the SFE and a fluorescence calibration standard to verify mechanical fit and absence of signal contamination. Design feedback was provided by pediatric dentists and staff engineers to guide iterations. The final design configuration was based on the need to image interproximal regions (contact surfaces between adjacent teeth), ergonomics, and probe safety. The final handpiece design: (1) is safe for both the patient and the probe, (2) allows easy SFE insertion and removal, (3) does not interfere with spectral measurements, (4) standardizes the SFE's positioning during imaging by maintaining a consistent distance from the target surface, and (5) is significantly less expensive to produce and use than purchasing sanitary endoscope sheaths. The device will be used to help determine if new medicinal therapies can arrest caries and repair early interproximal demineralization under the clinical monitoring program. Ultimately, we anticipate that this handpiece will help us move closer toward widespread implementation of a dental diagnostic laser system that is safer and more sensitive than conventional methods for early caries detection.