<p dir="ltr">Amphibians produce diverse bioactive compounds with reported antimicrobial and cytotoxic activities, yet their potential as anticancer agents remains underexplored. This study evaluated the antitumor efficacy of amphibian-derived skin extracts in a xenograft model. Sixty animals were randomly allocated to treatment or control groups and monitored for 12 weeks. Tumor progression was assessed by volumetric and gravimetric endpoints, while mechanistic insights were obtained through Ki-67 immunohistochemistry, TUNEL apoptosis assays, and quantitative RT-PCR profiling of p53, Bax, Bcl-2, Caspase-3, and Ki-67. Treated animals developed significantly smaller tumors compared with controls, with reduced volume (120.5 ± 3.8 mm³ vs. 180.2 ± 4.3 mm³; p = 0.005) and mass (0.62 ± 0.08 g vs. 0.93 ± 0.09 g; p = 0.005). Histological analyses revealed a lower proliferation index (25.5% vs. 40.3%) and a higher apoptotic index (35.0% vs. 19.0%), both of which were statistically significant. At the molecular level, expression profiling revealed the upregulation of p53, Bax, and Caspase-3, accompanied by the downregulation of Bcl-2 and Ki-67, which aligns with the observed tissue phenotypes. Taken together, these results provide convergent evidence that amphibian-derived extracts exert multifaceted antitumor effects, inhibiting proliferation and promoting apoptosis. Although further studies are required to characterize active constituents, establish pharmacological profiles, and validate efficacy in mammalian models, the findings support amphibian-origin compounds as promising candidates for preclinical anticancer development.</p>