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The anticancer activities of <i>Rubia cordifolia</i> and its constituents have been reported earlier, but their influence on the crosstalk of complex cancer-related signaling metabolic pathways (i.e., transcription factors; TF) has not yet been fully investigated. In this study, <i>R. cordifolia</i> root extract was subjected to the cancer signaling assay based bioactivity-guided fractionation, which yielded the following compounds viz., three anthraquinones, namely alizarin (<b>1</b>), purpurin (<b>2</b>), and emodin (<b>3</b>); two lignans, namely eudesmin (<b>4</b>) and compound <b>5</b>; and two cyclic hexapeptides, namely deoxybouvardin RA-V (<b>6</b>), and a mixture of <b>6</b>+<b>9</b> (RA-XXI). The structures of the isolated compounds were determined by NMR spectroscopy and HRESIMS. The isolated compounds <b>1</b>, <b>2</b>, <b>3</b>, <b>6,</b> and a mixture of <b>6</b>+<b>9</b> were tested against a panel of luciferase reporter genes that assesses the activity of a wide-range of cancer-related signaling pathways. In addition, reference anthraquinones viz., chrysophanol (<b>11</b>), danthron (<b>12</b>), quinizarin (<b>13</b>), aloe-emodin (<b>14</b>), and α-lapachone (<b>15</b>) were also tested. Among the tested compounds, the cyclic hexapeptide <b>6</b> was found to be very active against several signaling pathways, notably Wnt, Myc, and Notch with IC₅₀ values of 50, 75, and 93 ng/mL, respectively. Whereas, the anthraquinones exhibited very mild or no inhibition against these signaling pathways. Compound <b>6</b> being the most active, we tested it for stability in simulated intestinal (SIF) and gastric fluids (SGF), since the stability in biological fluid is a key short-coming of cyclic hexapeptides. The anticancer activity of <b>6</b> was found to remain unchanged before and after the treatment of simulated gastric/intestinal fluids, indicating that RA-V was stable. As a result, it could be bioavailable when orally used in therapeutics and possibly a drug candidate for cancer treatment. The mechanism for the preferential inhibition of these pathways and the possible crosstalk effect with other previously reported signaling pathways has been discussed.