Cancer remains a significant challenge, prompting exploration of new therapies. Breast cancer is the most prevalent among women, and current medications often have serious side effects. Additionally, there's limited research on natural resources that historically provided bioactive compounds with potential anti-cancer properties. This study examines two such resources: Cannabis sativa and Datura metel L., both known for their pharmacological diversity and traditional medicinal use. Cannabis sativa, with its major constituents Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), has garnered considerable interest. Datura metel L., despite its toxicity, contains alkaloids like scopolamine and withametelin, which have shown cytotoxic properties against cancer cells. This study selected five breast cancer-related receptors, docking them against various phytoconstituents in both plants to identify potent cytotoxic entities. Target proteins were extracted from the PDB database, and docking studies were performed using AutoDock software. The docking scores of the phytochemicals were then compared with each other. The docking studies on Cannabis sativa revealed that apigenin (-8.15), β-caryophyllene oxide (-8.35), THCA (-8.84), epicatechin (-8.18), and vitexin (-9.58) showed good interaction with the PARP receptor (PDB ID: 5DS3), while cannabidiol (-8.38) and cannabichromene (-8.36) showed strong interactions with CDK4/6 (PDB ID: 6GS7). Additionally, strychnine (-9.99), naringin (-9.19), and luteolin (-8) demonstrated good interactions with the estrogen receptor (PDB ID: 3ERT). In the case of Datura metel L., withametelin (-10.69) and dinoxin B (-10.72) showed good interactions with the estrogen receptor (PDB ID: 3ERT), and scopolamine (-8.24) with CDK4/6 (PDB ID: 6GS7). These findings suggest that these phytoconstituents possess anticancer activities.