Objectives: Oral cancer is a leading cause of mortality in India, yet rural populations face severe barriers to its early detection. This study evaluates the efficacy of a novel, portable optical screening device (OncoDiagnoScope) and assesses demographic risk factors in a resource-limited setting. Methods: This community-based cross-sectional study (N = 1358; mean age 51.8 ± 13.7 years) was conducted in rural Tamil Nadu. Participants underwent a multitiered screening protocol: initial assessment via OncoDiagnoScope, secondary clinical evaluation by specialists, and histopathological confirmation for suspicious lesions. Risk factors were analyzed using univariate and multivariate logistic regression. Results: The OncoDiagnoScope identified 321 suspects (23.6%), of which 101 (7.4%) were clinically confirmed as having oral lesions and nine cases (0.66%) were histopathologically confirmed as malignancies. The device demonstrated a sensitivity of 100%, specificity of 82.14%, and a negative predictive value (NPV) of 100% compared to expert clinical examination. While univariate analysis showed significant associations between lesions and age (P = 0.040), tobacco chewing (P = 0.009), and betel leaf use (P = 0.002), these variables were not independent predictors in the multivariate adjusted model (Pseudo-R2 = 0.027). Conclusion: The OncoDiagnoScope is a highly sensitive, non-invasive tool for community-level oral cancer triaging. Despite a low positive predictive value (31.46%), its ability to accurately rule out disease (NPV 100%) makes it an ideal aid for rural outreach. Integrating portable diagnostic technologies into existing health-wellness programs can significantly bridge the gap in early cancer detection for marginalized populations.