Plants have proved to be an important source of anti-cancer drugs. Here we have investigated the anticancer activity of the herbal formulation Shemamruthaa in rat models. SM contains multiple phenolic compounds and secondary metabolites that contribute to their biological properties. Female Sprague Dawley rats of 180 ± 10 g were categorized into four groups. Two groups were administered DMBA (25 mg/rat, orally) dissolved in olive oil to induce mammary carcinoma. One of these groups received Shemamruthaa (SM) (400 mg/ kg b.wt, orally) for 14 days after 90 days of DMBA induction. A vehicle treated control and drug control groups were also included. The status of oxidative stress markers, DNA fragmentation and western blot analysis of PCNA, p53, Bax, Bcl-2 and caspases were carried out in control and experimental rats. Our findings revealed that the SM formulation induced cell death was considered to be apoptotic by observing the typical DNA ladder formation on electrophoresis. The results of western blot analysis established the down-regulation of cell proliferative PCNA, anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic proteins like p53, Bax and caspases expressions in mammary tissues of SM treated cancer bearing animals. Our results demonstrate that SM can inhibit cancer cell proliferation and induce apoptosis via p53-dependent mechanism. Our findings indicate that SM contains potential anti-cancer agents acting either singly or in combination against breast cancer cell proliferation.