Cancer is a global health challenge, with increasing cases and related deaths. Ehrlich Ascites carcinoma (EAC) is a well-established cancer model. Purslane (Portulaca oleracea L.) is a studied plant rich in bioactive compounds, including antioxidants, making it relevant in cancer research. Doxorubicin (DOX), a common anticancer drug, has potent effects but severe side effects. This study investigated the anti-tumor potential of Purslane seed oil methanolic extract (PSO) and its synergistic effects with the common anticancer drug doxorubicin (DOX) in EAC-bearing mice (n=64). Animals were randomized into eight groups (8/group): control, PSO alone, DOX alone, PSO+DOX, EAC control, EAC+PSO, EAC+DOX, and EAC+PSO+DOX. Following intraperitoneal injection of EAC cells (2x10⁶), mice received 3 weeks of treatment with PSO (200 mg/kg/day) and DOX (4 mg/kg/week). PSO and DOX treatment alone demonstrated anti-tumor activity, with their combination exerting a synergistic effect. The PSO and DOX combination showed stronger anti-tumor effects, restoring antioxidant levels, reducing reactive oxygen species, and decreasing inflammation. PSO induced EAC cell apoptosis, increasing apoptotic marker caspase-3 and decreasing anti-apoptotic gene Bcl-2 expression. PSO and DOX significantly reduced EAC proliferation. In conclusion, PSO suppresses EAC tumor growth by improving oxidative balance, reducing inflammation, inducing apoptosis, and inhibiting proliferation. Further research is needed to clarify mechanisms and confirm its effectiveness against solid cancers as a dietary or medicinal agent.