Background/Objectives: Oral cancer (OC) is a disease with poor prognosis mainly due to late diagnosis. There is considerable interest in the use and development of rapid, point of care (POC) non-invasive methods that can accelerate the diagnostic process. Bioimpedance (BI) is resistance to the passage of electric currents through tissue that reflects structural changes in the tissue. The aim of this study was to determine the spectrum of BI values in patients with oral cancer, to compare them with other oral lesions and healthy controls, and to determine the diagnostic value of the BI-based method for diagnosis of OC. Methods: Ninety-three participants divided into three groups participated in this study. The first group (31 participants) consisted of patients with histologically confirmed OC, the second group (31 participants) consisted of patients with an active reticular form of oral lichen planus (positive controls; OLP) and the third group (31 participants) consisted of healthy controls. In OC and OLP patients, BI was measured at three points (non-ulcerated lesional mucosa, clinically unaffected perilesional mucosa and unaffected mucosa on the contralateral side). In healthy controls, BI was measured on a healthy mucosa in the corresponding anatomical region. Measurements were performed at nine frequencies (1, 2, 5, 7, 10, 20, 70 and 100 kHz). Results: In OC patients, BI values in the lesion were significantly lower than BI values in clinically intact perilesional mucosa and the unaffected contralateral side at all frequencies. Furthermore, BI values of the clinically intact perilesional mucosa were significantly lower than the BI values of the healthy contralateral mucosa at frequencies of 1 kHz, 2 kHz, 5 kHz, 7 kHz and 10 kHz. Patients with OC had significantly lower BI values compared to patients with OLP and individuals with healthy oral mucosa at all frequencies. Conclusions: This study demonstrated the very good to excellent ability of this method to detect OC lesions, which needs to be confirmed by further studies on a larger number of participants.