Purpose Oral squamous cell carcinoma (OSCC) and oral potentially malignanant disorders (OPMDs) are characterized by various mutations in the cells. These mutations lead to electrochemical changes at cellular level which in turn are responsible for lower bioimpedance of the tissue. The aim of this study was to determine the bioimpedance of OSCC, OPMDs and normal oral mucosa, in order to establish a new approach for reliable, low-cost, noninvasive, and real-time screening of OSCC and OPMDs. The objectives were to determine and compare the bioimpedance of OSCC, OPMDs and normal oral mucosa and to correlate the bioimpedance of OSCC with its TNM stage and histopathologic grade. Material and Methods Thirty OSCC, 40 OPMD patients (10 leukoplakia, 10 erythroplakia, 10 oral submucous fibrosis and 10 oral lichen planus) and 10 healthy subjects were recruited in this study. A silver probe connected to an impedance analyzer was used to determine the bioimpedance of OSCC, OPMDs and normal oral mucosa at different frequencies with a voltage limited to 200 mV. Results Bioimpedance of OSCC, OPMDs and control group decreased as frequency increased. The impedance of OSCC was less than that of OPMDs and control group. The impedance of OSCC was found to be significantly smaller than that of OPMDs and control group at 20 Hz and 50 kHz. Moreover, as the grade of malignancy or dysplasia increased, bioimpedance decreased. Bioimpedance of OPMDs was smaller than in control group. Moreover, in leukoplakia, erythroplakia and OSMF, it was found to be significantly smaller than that of control group at 20 Hz and 50 kHz. The impedance of lichen planus was smaller than that of control group at 20 Hz and 50 kHz but was statistically insignificant. Conclusions In conclusion, bioimpedance at particular frequencies is a potentially promising technique for detection of OSCC and OPMDs and can be used in primary care centers or in the developing countries with minimal expertise.