Background: Parotoid gland secretions (PGS) contain several bioactive compounds with potential applications for drug development. Objective: This study was conducted to evaluate the in vivo antitumor effect of PGS collected from the Egyptian toad, Bufo relgularis using Ehrlich ascites carcinoma-bearing mice (EAC). Methods: The median lethal dose (LD₅₀) of PGS was determined, then forty CD-1 female mice were divided into 4 groups (n=10) as follows: Group (Gp1) served as a negative control. Gp2-Gp4 had inoculated intraperitoneally (i.p) with 1×10⁶ EAC cells/mouse. Then, Gp2 was left as a positive control (EAC- bearing mice). After 24 hours, Gp3 had injected i.p with Cisplatin (Cis) (2 mg/kg) on day 1 for 7 consecutive days. Gp4 had injected with 1/10 LD₅₀ of PGS (7.85 mg/kg, b.wt) i.p for 7 consecutive days. All groups were sacrificed on day 14 to collect blood samples. The percentages of total body weight (% bwt) change, tumor volume, and total tumor cell counts were determined. Alanine and aspartate transaminases (ALT and AST), antioxidant /oxidant biomarkers (SOD, CAT, and MDA), and histological investigations of liver tissues were evaluated. Results: The results showed that the % b.wt changes were increased in EAC- bearing mice, while the treatment of EAC- bearing mice with PGS decreased its % b.wt changes. The treatment of EAC- bearing mice with PGS decreased the tumor volume and its counts. PGS treatment led to an improvement in AST, ALT, and antioxidant enzyme activities, and ameliorated the histopathological changes in the liver induced by EAC inoculation. Conclusion: We concluded that PGS had a potential anticancer effect against EAC- bearing mice.