Adriamycin (ADR) is a frequently employed chemotherapeutic agent for the management of breast cancer. Nevertheless, multidrug resistance (MDR) can impair its therapeutic efficacy in breast cancer. MDR is characterized by increased expression of the P‐glycoprotein (P‐gp) efflux pump, up‐regulation of anti‐apoptotic proteins, and downregulation of pro‐apoptotic proteins. Consequently, inhibition of ATP‐binding cassette (ABC) transporter proteins has been deemed the most efficacious approach to overcome MDR. In this study, we used MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide), Western blots, flow cytometry, immunofluorescence, and constructed xenograft tumors to investigate whether ginsenoside Rg3‐near‐infrared photothermal (Rg3‐NIR) combination reversed multidrug resistance in MCF‐7/ADR breast cancer. In vivo and in vitro experiments, the results showed that Rg3‐NIR co‐treatment was effective in inducing the apoptosis of MCF‐7/ADR breast cancer cells. This was achieved by reversing the expression of drug resistance‐associated proteins, while also inhibiting cell proliferation, migration, and epithelial–mesenchymal transition (EMT) processes via attenuation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) signaling pathway transduction. Ginsenoside Rg3 combined with near‐infrared photothermal therapy (NIR) effectively reverses multidrug resistance in breast cancer MCF‐7/ADR cells, providing a new therapeutic strategy for breast cancer drug resistance.