Background: The aim of this study was to investigate diffusion-weighted imaging (DWI) in the oral and maxillofacial region, with a special focus on the usefulness of apparent diffusion coefficient (ADC) maps and maximum intensity projection (MIP) for characterization of normal structures and lesions. Material/Methods: Thirty-five patients who underwent magnetic resonance imaging (MRI) for diagnosis of oral and maxillofacial lesions were included in this prospective study. DWI was performed on a 1.5 T unit, with b factor of 0 and 800 s/mm2; moreover, ADC maps were generated. ADC values were measured for normal structures, odontogenic infections, squamous cell carcinomas (SCC), and hemangiomas. Results: As regards the normal structures, the mean ADC value of the cerebrospinal fluid (3.65±0.60×10-3 mm2/s) in the upper neck area was higher than that of the spinal cord (0.74±0.15×10-3 mm2/s, P=0.000), lymph nodes (0.87±0.17×10-3 mm2/s, P=0.000), and Waldeyer’s ring (0.92±0.29×10-3 mm2/s, P=0.000). The mean ADC value of hemangiomas (1.52±0.31×10-3 mm2/s) was higher than that of odontogenic infections (0.85±0.36×10-3 mm2/s, P=0.034) and SCC (1.38±0.22×10-3 mm2/s, P=0.840). Furthermore, MIP (DWI) showed the normal structures and lesions in the oral and maxillofacial region in an improved way. Conclusions: DWI, ADC maps, and MIP can be used to characterize and differentiate normal structures and lesions in the oral and maxillofacial region.