Oral squamous cell carcinoma remains a pressing issue due to high incidence, late diagnosis, and limited effectiveness of standard treatments with severe toxic effects. This study compared the antitumor activity and safety of Curcuma longa, Camellia sinensis, and Nigella sativa extracts in a rat model of DMBA-induced oral cancer. The experiment involved 78 adult male Wistar rats. Acute toxicity was assessed at 5000 mg/kg. Tumors were induced by applying 0.5% DMBA to the buccal mucosa three times weekly for 16 weeks. Animals received saline, plant extracts (500 mg/kg each), or cisplatin (2 mg/kg) for 8 weeks. Tumor measurements were performed weekly. Histological, immunohistochemical (Ki-67, caspase-3), and biochemical analyses were conducted. All extracts showed antitumor activity without toxicity. Black cumin extract demonstrated the highest efficacy, reducing tumor incidence to 70% (vs. 100% in controls) and decreasing tumor volume 2.8-fold (650 vs. 1850 mm³), achieving 64.9% growth inhibition. Immunohistochemistry revealed decreased Ki-67 to 31.4% (vs. 68.3%) and increased caspase-3 to 34.2% (vs. 8.2%), approaching cisplatin values (28.7% and 38.5%). Turmeric and green tea extracts showed moderate effects with 80% incidence and 47.0-52.4% inhibition. Cisplatin caused significant hepato- and nephrotoxicity, while plant extracts maintained normal parameters. All extracts suppress proliferation and induce apoptosis. Black cumin extract showed cisplatin-comparable efficacy without toxicity, supporting its further investigation for oral cancer management.