This study further expands current knowledge by highlighting isorhamnetin’s ability to modulate biotransformation enzymes and drug efflux transporters involved in drug resistance in colon cancer cells, notably through the suppression of P-gp protein expression and reduction in CYP1A1, CYP1B1, MRP1, and MRP5 mRNA levels. Here, CYP1A1 is linked to malignant colon neoplasm.