Breast cancer has been one of the most common form of malignancy globally among women, for more than a decade. Despite various preventive and treatment measures, it remains associated with high incidence and mortality rate. Pterocarpus santalinus Linn. f. has been extensively used in Indian medicine system Ayurveda, due to its various medicinal properties. However, despite various research works on the anticancer activity of P santalinus, no studies have been reported on animal model. Therefore, this study was aimed to decipher the antitumour activity of ethanolic seeds extract of P santalinus on DMBA (7,12-dimethylbenz(a)-anthracene)-induced breast cancer in rats. Fifty-five-days-old weighed (150 ± 10 g) female Charles Foster rats (12 females) were used for the study. The rats were divided into 3 groups of 4 rats each. 7,12-Dimethylbenz(a)-anthracene (single dose of 20 mg/mL dissolved in olive oil) was induced orally, to develop breast tumour. After the development of breast tumours (about 0.5 cm), the rats were treated with P santalinus ethanolic seeds extract (300 mg/kg body weight/day) orally for 5 weeks and then volume of tumour was measured. Oral administration of P santalinus extract resulted in about 49.5% tumour growth inhibition in the final week of treatment in DMBA + P santalinus group as compared with the DMBA group. Pterocarpus santalinus administration also significantly reduced (P < .0001) the serum malondialdehyde level from 58.81 ± 4.09 nmol/mL in DMBA group to 10.87 ± 1.20 nmol/mL in the DMBA + P santalinus group. Serum tumour necrosis factor-α level reduced significantly (P < .0001) from 80.43 ± 2.45 pg/mL in DMBA group to 28.30 ± 3.24 pg/mL in the DMBA + P santalinus group. The blood serum glucose level also reduced significantly (P < .0001) from 205.9 ± 22.22 mg/dL in DMBA group to 86.44 ± 8.36 in DMBA + P santalinus group. There was significant (P < .0001) improvement in the both the liver and kidney serum biomarkers level after P santalinus administration. The histological study of mammary tissues of rats shows that, in the DMBA group immature fibrocytes are completely replacing the normal adipocytes suggestive of fibroma molle, whereas in the DMBA + P santalinus group mature fibrocytes with multilayer glandular cells were seen denoting fibroadenoma. Thus, the P santalinus ethanolic seed extract possesses antitumorigenic, antioxidant and hypoglycaemic properties as well as hepato-renal protective effect. Hence, it may be concluded that P santalinus has therapeutic role against DMBA-induced breast cancer in rats and has a greater potential to develop as a chemotherapeutic agent in breast cancer treatment.