Previous studies suggest that craniofacial manual lymphatic drainage (MLD) facilitates brain fluids clearance, reducing intracranial pressure and reabsorbing chronic subdural hematoma. This study aimed to explore the effect of craniofacial MLD in combination with pharmacological treatment for improving cranial pain intensity, vital signs, and cerebral edema (Hounsfield units, HUs) in moderate traumatic brain injury (mTBI). Patient 1 received pharmacological therapy, while patient 2 received both pharmacological and craniocervical MLD treatment. Patient 2 showed decreased cranial pain intensity and systolic blood pressure (66%–11.11%, respectively) after two 30 min daily sessions of treatment for three days. HUs in the caudate nucleus of both hemispheres (left 24.64%–right 28.72%) and in the left temporal cortical gray matter increased (17.8%). An increase in HU suggests a reduction in cerebral edema and vice versa. For patient 1, there were no changes in cranial pain intensity, but a slight increase in the systolic blood pressure was observed (0%–3.27%, respectively). HUs decreased in the temporal cortical (14.98%) and caudate nucleus gray matter (9.77%) of the left and right cerebral hemispheres (11.96%–16.74%, respectively). This case study suggests that craniofacial MLD combined with pharmacological treatment could reduce cerebral edema, decrease head pain intensity, and maintain vital signs in normal physiologic values in patients with mTBI.